Showing papers in "Medical Oncology in 2010"

Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells.

Abstract: The medicinal properties of curcumin are well documented in Indian and Chinese systems of medicine, which refer to its wide use in the treatment of some diseases. It has shown to have anti-carcinogenic properties and is known to prevent tumor development in some cancers. In our study, we confirmed that the expression of miR-15a and miR-16 was upregulated and that of Bcl-2 was downregulated in curcumin-treated MCF-7 cells. Silencing miR-15a and miR-16 by specific inhibitors restored the expression of Bcl-2. Thus, we concluded that curcumin can reduce the expression of Bcl-2 by upregulating the expression of miR-15a and miR-16 in MCF-7 cells.

The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinoma.

Abstract: Objective The mammalian target of rapamycin (mTOR) pathway, an important regulator of multiple cellular functions including proliferation, differentiation, tumorigenesis, and apoptosis, is up-regulated in many cancers. It has achieved considerable importance. This study was conducted to determine the status of the mTOR pathway in human hepatocellular carcinoma (HCC) and to investigate its relationship with the prognosis of HCC. Methods PTEN, pAkt, p27, and pS6 expression in cryo-sections gathered from 528 cases with HCC by the method of immunohistochemistry. Kaplan–Meier survival and Cox regression analyses were performed to evaluate the prognosis of HCC. Results The mTOR pathway was more significantly altered in high-grade tumors, and tumors with poor prognostic features. Especially, pAkt and cytoplasmic p27 expression showed the strongest associations with pathological parameters of HCC. Statistical analysis showed that HCC patients expressing pAkt, PTEN, cytoplasmic p27, and pS6 have different overall survival rates relative to those not expressing these proteins. Cox multi-factor analysis showed that tumor differentiation (P = 0.006), vascular invasion (P = 0.028), TNM stage (P = 0.005), pAkt (P = 0.021), PTEN (P = 0.003), p27 (P = 0.018) and pS6 (P = 0.002) were independent prognosis factors for HCC. Conclusion: Expression of the mTOR pathway components, which are related with the transferability and invasive capacity of HCC cells, may be used as prognostic indicators in HCC.

Depression and anxiety levels in woman under follow-up for breast cancer: relationship to coping with cancer and quality of life

Abstract: Aim The relation of anxiety and depression levels with characteristics of coping with the disease and quality of life were evaluated in women under follow-up for breast cancer. Materials and Methods Patients who had presented to the breast cancer polyclinics for follow-up were evaluated. The Beck Depression and the State-Trait Anxiety inventories were used in the evaluation of depression and anxiety levels. In order to evaluate their power to cope with cancer, the patients were questioned for a social support network. EORTC QLQ-C30 and QLQ-BR23 questionnaires were applied for quality of life evaluations. Results There were 23 (19%) patients with depression; 3 (2.5%) with grade I anxiety, 94 (77%) grade II, and 23 (19%) grade III anxiety, respectively. Depression and anxiety levels were affected by the following parameters: being unaccompanied by spouse for hospital follow-ups (P < 0.0001); request to get help by a psychologist (P = 0.02); presence of a person to share their problems (P < 0.0001); and using an alternative treatment (P = 0.04). In the quality of life evaluations, difficulty in sleeping, emotional status, fatigue, and body appearance were related with both depression and anxiety (P < 0.05 for all), whereas physical function (P = 0.002), role performance (P = 0.005), cognitive condition (P < 0.0001), social position (P < 0.0001), pain (P < 0.0001), general health (P < 0.0001), treatment methods (P = 0.001), future anxiety (P < 0.0001), and arm symptoms (P = 0.001) were negatively affected in patients with depression. Conclusion High depression and anxiety levels in patients under follow-up for breast cancer influence the coping with cancer and quality of life adversely.

The effect of peripheral blood values on prognosis of patients with locally advanced gastric cancer before treatment

Abstract: We aimed to investigate the prognostic significance of neutrophil, lymphocyte, platelet, mean platelet value (MPV), platelet-lymphocyte ratio (PLR) and neutrophil–lymphocyte ratio (NLR) in patients with locally advanced gastric cancer (LAGC). One hundred sixty-eight patients with LAGC who had been followed-up between 2004 and 2008 were included in present study. The results of hematological (platelet, lymphocyte, neutrophil and MPV) and biochemical (uric acid and LDH) parameters were evaluated before treatment. NLR was divided into two groups as 160. Platelet counts and lymphocyte counts were also divided into two groups; ≤300.000/mm3 and >300.000/mm3, and <1,500/mm3 and ≥1,500/mm3, respectively. Results were evaluated with Kaplan–Meier and Long-rank tests. The mean age of patients at diagnosis was 60.1 ± 12.1 and 114 of patients (67.8%) were male. For 168 patients, 48 months overall survival (OS) rate was 45.2% and the median OS was 39 months (range 33–44). In patients whose PLR was less than 160 (n = 54), the median OS was 45 months (range 38–52) and also for cases whose PRL was greater than 160 (n = 114), the median OS was 27 months (range 22–32) (p = 0.006). While for fifty patients whose lymphocyte counts were less than 1,500, the median OS was 27 months (range 21–33), in cases with high lymphocyte counts (≥1,500) (n = 118), it was 41 months (range 35–48) (p = 0.03). The median OS was 41 (range 34–48) and 30 (range 23–37) months in two platelets groups, respectively (p = 0.24). However, in the patients whose NLR was less than 2.56 (n = 107), median OS was better than with cases whose NLR was greater than or equal to 2.56 (42 vs. 27 months). Routine peripheral blood counts may be useful prognostic factor for evaluating the accuracy of risk stratification in patients with radically resected gastric cancer Our results need to be confirmed by study including larger sample size in future.

Down-regulation of miR-31 expression in gastric cancer tissues and its clinical significance

Abstract: MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of target mRNAs. Altered expression of specific miRNAs in several tumor types has been reported. However, the expression levels of miR-31 in gastric cancers are unclear. The objective of the present study was to compare the expression profile of miR-31 between gastric cancer tissues and non-tumor tissues. Real-time quantitative reverse transcription-polymerase chain reaction technology was used to detect the levels of miR-31 expression. The expression levels of miR-31 in gastric cancer tissues were significantly lower than those in non-tumor tissues. This new information may help to clarify the molecular mechanisms involved in gastric carcinogenesis and to indicate that miR-31 may be a novel diagnostic biomarker of gastric cancer.

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer

Abstract: The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), α-1 globulin, and α-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and α-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.

MicroRNA-9 reduces cell invasion and E-cadherin secretion in SK-Hep-1 cell.

Abstract: MicroRNAs (miRNAs) are an abundant class of short noncoding RNAs that can posttranscriptionally regulate gene expression in animals. They are also involved in cancer initiation and progression, and their expression profiles serve as phenotypic signatures of different cancers. The roles played by microRNAs specifically in “micromanagement of metastasis” has been addressed only recently. The molecular mechanisms of hepatocellular carcinoma (HCC) metastasis are still poorly understood. Recent evidence implies genetic determinants of cancer metastasis. Because gene expression signature significantly differs between primary metastasis-free HCC and primary HCC with intrahepatic metastases, miRNA expression in those primary HCC may change correspondingly. The 28 up-regulated miRNAs, part of the reported miRNA profiles of HCC, were compared in primary HCC with or without metastases. Only eight miRNAs were found to be significantly up-regulated in primary HCC with metastases while miR-9 had the highest hold change. miR-9 was highly expressed in SK-Hep-1 cell when compared with other hepatoma cell lines and downregulation of miR-9 reduced SK-Hep-1 cell invasion. E-cadherin, a tumor invasion suppressor in HCC, was found to be a putative gene target of miR-9. E-cadherin was up-regulated by miR-9 inhibitor. The findings suggest miR-9 could be involved in HCC metastasis.

A case-control study of reproductive factors associated with subtypes of breast cancer in Northeast China.

Abstract: Based on the expression of estrogen receptor (ER), progesterone receptor (PR) and HER2/neu (HER2), breast cancer is classified into several subtypes: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), HER2-overexpressing (ER-, PR-, and HER2+) and triple-negative (ER-, PR-, and HER2-). The aim of this case-control study is to determine reproductive factors associated with breast cancer subtypes in Chinese women. A total of 1,417 patients diagnosed with breast cancer in the First Affiliated Hospital, China Medical University, Shenyang, China between 2001 and 2009 and 1,587 matched controls without a prior breast cancer were enrolled. Personal interviews were conducted to obtain information on reproductive characteristics and clinical history. Relationships between the factors and the subtypes of breast cancer were examined using logistic regression to compute odds ratios (OR) and 95% confidence intervals (CI). Notably, luminal A (50.0%) was the most prevalent subtype relative to luminal B (15.10%), HER2-overexpressing (10.87%) and triple-negative (23.08%). Menarche at an early age was associated with a reduced risk of luminal A (OR, 2.35; 95% CI, 1.45-3.81). Breastfeeding protected parous women from any subtype of breast cancer. Postmenopause and spontaneous abortion were inversely associated with the risk of luminal tumors. By contrast, multiparity, family history of breast cancer and induced abortion increased the risk of breast cancer. Collectively, our findings suggest that reproductive factors such as age at menarche, parity, breastfeeding, menopausal status and abortion history have different effects on the subtypes of breast cancer in Chinese women.

TNF-alpha and its inhibitors in cancer.

Abstract: Tumor necrosis factor (TNF)-α is implicated in the same time in apoptosis and in cell proliferation. TNF-α not only acts as pro-inflammatory cytokine conducing to wide spectrum of human diseases including inflammatory diseases, but can also induce tumor development. The molecular mechanisms of TNF-α functions have been intensively investigated. In this review we covered TNF-α, the molecule, its signaling pathway, and its therapeutic functions. We provide a particular insight in its paradoxical role in tumor promotion and in its use as anti-tumor agent. This review considers also the recent findings regarding TNF-α inhibitors, their pharmacokinetics, and their pharmacodynamics. Six TNF-α inhibitors have been considered here: Infliximab, Adalimumab, Golimumab, CDP870, CDP571, Etanercept, and Thalidomide. We discussed the clinical relevance of their functions in treatment of several diseases such as advanced inflammatory rheumatic and bowel disease, with a focus in cancer treatment. Targeting TNF-α by these drugs has many side effects like malignancies development, and the long-term sequels are not very well explored. Their efficacy and their safety were discussed, underscoring the necessity of close patients monitoring and of their caution use.

Systematic analysis of microRNA involved in resistance of the MCF-7 human breast cancer cell to doxorubicin

Abstract: Multidrug resistance remains a major clinical obstacle to successful treatment of breast cancer and leads to poor prognosis for the patients. Recently studies have shown that microRNAs play an important role in breast cancer cell resistance to chemotherapeutic agents. In this study, microRNA expression profiles of MCF-7/AdrVp and MCF-7 were analyzed using microarray and the results were confirmed by real-time RT-polymerase chain reaction. Gene Ontology (GO) and pathways mapping tools were employed to analyse systemically the biological processes and signaling pathways affected by differential expression microRNAs. Here, we showed that 181 human microRNAs were differentially expressed between two cell lines. Compared to MCF-7 cells, there were 16 microRNAs down-regulated and 165 microRNAs up-regulated in MCF-7/AdrVp. Western blot confirmed the correlation between specific microRNA expression and corresponding changes in protein levels of their targets, specifically those that have a documented role in cancer drug resistance. Furthermore, we validated that signaling pathway highlighted in the study was involved in drug resistance. These results indicated that breast cancer cell resistant to chemotherapy was associated with a group of microRNAs. GO and pathway mapping are valid and effective approach to analyse the function of microRNAs and the results could be a guideline for further investigation.

Inhibition of Notch3 enhances sensitivity to gemcitabine in pancreatic cancer through an inactivation of PI3K/Akt-dependent pathway.

Abstract: Notch3 is one of the four Notch receptors identified in mammal, but its role in human pancreatic cancer remains poorly characterized. In this study, we sought to determine the effect of suppressing Notch3 expression on the chemosensitivity to gemcitabine in human pancreatic cancer cell lines BxPC-3 and PANC-1. RNA interference was used to suppress Notch3 expression. Gemcitabine-induced cytotoxicity was determined by MTT. Cell apoptosis was measured by flow cytometry. Caspase 3 activity was assayed using a Caspase Fluorescent Assay Kit. The effect of Notch3-specific siRNA on PI3K/Akt activity was also quantified. Notch3-specific siRNA suppressed Notch3 expression, and furthermore increased gemcitabine-induced, caspase-mediated apoptosis. The suppression of Notch3 expression decreased the average IC50 in BxPC-3 and PANC-1 cells treated with gemcitabine. PI3K/Akt activity was decreased by the suppression of Notch3 expression. Taken together, these data demonstrated that Notch3 is a potential therapeutic target for pancreatic cancer, and PI3K/Akt is a key signaling component by which activation of the Notch3 signal transduction pathway protects pancreatic cancer cells from chemotherapy-induced cell death.

Growth inhibition and cell-cycle arrest of human gastric cancer cells by Lycium barbarum polysaccharide

Abstract: Lycium barbarum polysaccharide (LBP) is extracted from the traditional Chinese herb Lycium barbarum, and has potential anticancer activity. However, the detailed mechanisms are largely unknown. The purpose of this study was to observe the anticancer effect of LBP on human gastric cancer, and its possible mechanisms. Human gastric cancer MGC-803 and SGC-7901 cells were treated with various concentrations of LBP for 1-5 days, and cell growth was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Distribution of the cell cycle was analyzed by flow cytometry. Western blotting was used to indicate changes in the level of cyclins and cyclin-dependent kinases (CDKs). LBP treatment inhibited growth of MGC-803 and SGC-7901 cells, with cell-cycle arrest at the G0/G1 and S phase, respectively. We believe that this is the first study to show that LBP arrested different cell lines from the same types of cancer at different phases. The changes in cell-cycle-associated protein, cyclins, and CDKs were consistent with the changes in cell-cycle distribution. This study suggests that induction of cell-cycle arrest participates in the anticancer activity of LBP on gastric cancer cells.

Infections in acute myeloid leukemia: an analysis of 382 febrile episodes

Abstract: Neutropenic fever is an important cause of morbidity and mortality during therapy of acute myeloid leukemia (AML). We retrospectively analyzed 382 febrile episodes encountered during induction and consolidation chemotherapy to determine the potential etiology, microbiologic spectrum, response/resistance to antibiotics and outcome. Between May, 2001 and December, 2006, 95 patients with de novo non-M3 AML received remission induction chemotherapy followed by consolidation in those who achieved complete remission. Patients median age was 28 years, ranging from 2 to 61 years, 26 patients were ≤15 years of age. There were 57 males and 38 females. Febrile neutropenia was defined as per international guidelines. A total of 382 febrile episodes were recorded; neutropenic 347 (induction phase 172, consolidation phase 175) and non-neutropenic 35 (induction 16, consolidation 19). Clinical, microbiological and radiological evidence of infection could be identified in 64% of the febrile episodes (74% during induction, 52% during consolidation). Pulmonary infections were most common, both during induction and consolidation phase. Microbiologically gram-negative infections predominated. There were 60 possible/probable/definite episodes of fungal infection. Six cases of tuberculosis (pulmonary 5 and spine 1) and 3 cases of malaria (including one case of cerebral malaria) were also identified. Nineteen patients died (17 during induction, 2 during consolidation); 17 deaths were infection related, 12/17 possibly due to fungal infections. We suggest that evaluation of antibacterial resistance patterns in an institution must be done routinely in order to choose empiric antibiotics therapy. Careful selection of antibiotics and early institution of antifungal therapy besides considering alternative diagnosis peculiar to the region (e.g. tuberculosis, malaria) may help in reducing morbidity and mortality during AML therapy.

mTOR/p70S6K Signal transduction pathway contributes to osteosarcoma progression and patients’ prognosis

Abstract: The mTOR/p70S6K signal transduction pathway plays a key role in the regulation of cancer cells’ survival and proliferation. However, its roles in osteosarcoma, which is one of the most rapidly growing sarcomas, remain unknown. This study investigated for the first time the correlation between the mTOR/p70S6K signal transduction pathway in human osteosarcoma and patients’ prognosis. The expression patterns of mTOR and p70S6K in paraffin-embedded specimens gathered from 65 patients with primary osteosarcoma were detected by the method of immunohistochemistry using antibodies against mTOR and p70S6K. Kaplan–Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Immunostaining revealed that the mTOR/p70S6K signal transduction pathway is activated in human osteosarcoma. Additionally, positive expression of mTOR and p70S6K proteins was significantly correlated with surgical stage, metastasis pattern and percentage of dead cells of osteosarcoma. Moreover, in univariate analysis, surgical stage, metastasis pattern and percentage of dead cells, mTOR and p70S6K expression showed significant influence on overall survival (OS) and disease-free survival (DFS). In multivariate analysis, surgical stage (IIA vs. IIB/III), metastasis pattern (without vs. with), percentage of dead cells (≥90 vs. <90%), mTOR expression pattern (negative vs. positive) and p70S6K expression pattern (negative vs. positive) were significant for DFS and OS. Our results demonstrate the correlation of mTOR and p70S6K expression patterns with the oncological progression of osteosarcoma patients, suggesting the prognostic significance of the mTOR/p70S6K signal transduction pathway in osteosarcoma patients, which may lay a foundation for making further investigations on the mTOR/p70S6K signal transduction pathway as a potential target for osteosarcoma therapy.

GP73, a resident Golgi glycoprotein, is sensibility and specificity for hepatocellular carcinoma of diagnosis in a hepatitis B-endemic Asian population

Abstract: Golgi protein-73 (GP73) is a newly identified candidate serum marker for HCC, but GP73 study now is lesser in Asian population. The aims of this study were to determine how GP73 is detected in the serum of healthy, hepatitis B, cirrhosis and HCC by western blotting and RT-PCR, and to establish the sensitivity and specificity of serum GP73 protein and RNA for diagnosing HCC. Serum GP73 was detected by western blotting and RT-PCR, and quantified by densitometric analysis. GP73 was measured in serum from 124 patients with various forms of liver. AFP was tested using commercially available electrochemiluminescence immunoassay. The median sGP73 in patients with HBV-related HCC was significantly higher (P < 0.001) than in healthy individuals and in patients with other diseases. When sGP73 protein was used to detect HBV-related HCC, it had a sensitivity of 77.4% and a specificity of 83.9%, at the optimal cut-off value of 7.4 relative units. The area under the receiver-operating characteristic curve was 0.89. GP73 RNA in patients with HBV-related HCC had a sensitivity of 87.1% and a specificity of 83.9% and AUROC of 0.92. AFP in patients with HCC had a sensitivity of 48.4% and a specificity of 96.8% and AUROC of 0.77. GP73 protein and RNA can be found in the serum of patients with HBV-related HCC obviously higher than of other liver diseases in Asian. GP73 was better than AFP for the diagnosis of HBV-related HCC. RT-PCR is a more sensitive and superior method of quantification than Western blot. Furthermore, our data need to be confirmed in larger cohorts of patients.

CD8+CD28− cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients

Abstract: Aim To evaluate the CD8+CD28− and CD4+CD25+ regulatory T (Treg) cells in addition to other some lymphocyte subgroups in peripheral blood of advanced stage lung cancer patients. Methods The study group (n = 28) comprised chemotherapy and radiotherapy naive patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The control group (n = 22) consisted of age- and sex-matched healthy volunteers. Flow cytometry was used to count T cells, natural killer (NK) cells and CD4+CD25 Treg cells, and for CD8+ T cell subgroup analysis. Flow cytometry was performed and annexin V binding was used for apoptotic cell evaluation. Results In patient group, the percentage of CD8+CD28− cells among lymphocytes was elevated, and there was also an increase in the CD28−/CD28+ cell ratio among CD8 lymphocyte population. The distribution of CD8 cells was different in lung cancer patients when compared with the control group. The absolute count of CD4+CD25bright cells and the percentages of these cells among total lymphocytes were higher in the patient group. The Annexin V(+) cell percentages among CD8+CD28− and CD8+CD28+ lymphocytes were higher in the patient group than in the control group. No differences were found between the NSCLC and SCLC patients with respect to the hematological parameters and the distribution of lymphocyte subgroups. In NSCLC patients, the percentage of CD8+CD28− cells among the lymphocyte population was higher in patients with stage IV than those with stage III. Conclusion These findings may reflect the possibility of tumor-induced immunosuppression and they should be complemented with further studies.

Clinical outcome of patients with docetaxel-resistant hormone-refractory prostate cancer treated with second-line cyclophosphamide-based metronomic chemotherapy.

Abstract: For patients with docetaxel-resistant hormone-refractory prostate cancer (HRPC) no standard chemotherapeutic treatment exists. In this study, we evaluate the efficacy of cyclophosphamide (CP)-based metronomic chemotherapy in this patient population. Patients with metastatic HRPC with disease progression under docetaxel-based chemotherapy were eligible. The primary endpoint was prostate-specific antigen (PSA) response. Secondary endpoints were survival and toxicity. Low-dose CP (50 mg/d) and dexamethasone (1 mg/d) were administered orally in a metronomic manner. Treatment was continued until disease progression or intolerable side effects occurred. Seventeen patients were enrolled in this study. The median follow-up was 12 weeks (range: 4–60). Median age was 68 years (range: 42–85). Median PSA at study entry was 134 ng/ml (range: 46.0–6554). Nine patients had a PSA response (median 44.4%), four patients ≥50% and five patients <50%. Eight patients had a PSA progression. Overall survival was 24 months. Five patients reported a decrease in bone pain after 4 weeks' treatment. No grade 3 and 4 toxicities were noted. In this study, low-dose metronomically administered CP demonstrated efficacy as a second-line treatment in patients with docetaxel-resistant HRPC. The treatment was well tolerated and almost without toxicity. Further advantages of low-dose CP were its convenient oral administration, dosing schedule, low cost, and low-toxicity profile. These attributes in combination with immunoregulatory and antiangiogenic potentials make CP also a prime candidate for combination with other treatment regimens.

Evaluation of burnout syndrome in oncology employees.

Abstract: Burnout is an important occupational problem for health care workers. We aimed to assess the burnout levels among oncology employees and to evaluate the sociodemographic and occupational factors contributing to burnout levels. The Maslach Burnout Inventory, which is designed to measure the three stages of burnout-emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA), was used. The study sample consisted of 90 participants with a median age of 34 (range 23–56). The mean levels of burnout in EE, DP and PA stages were 23.80 ± 10.98, 5.21 ± 4.99, and 36.23 ± 8.05, respectively, for the entire sample. Among the 90 participants, 42, 20, and 35.6% of the employees had high levels of burnout in the EE, DP, and PA substage, respectively. Sociodemographic and occupational factors associated with higher levels of burnout included age of less than 35, being unmarried, being childless, >40 work hours per week, working on night shifts, and <10 years experience in the medicine/oncology field. Within all oncology clinics, medical oncology employees had the highest levels of burnout. Furthermore, employees who are not pleased with working in oncology field, who would like to change their speciality if they have an opportunity, and whose family and social lives have been negatively affected by their work experienced higher levels of burnout. Burnout syndrome may influence physical and mental health of the employee and affects the quality of health care as well. Therefore, several individual or organizational efforts should be considered for dealing with burnout.

Polycomb group protein Bmi1 expression in colon cancers predicts the survival

Abstract: Colorectal cancer is the second leading cause of cancer-related death in the United States and the fourth leading cause worldwide. Currently, there is still no excellent predictor of the survival. Polycomb-group proteins Bmi1 is regarded as a “stemness” gene involved in the maintenance of stem cells, malignant transformation, and biologic aggressiveness of several human carcinomas. We examined the expression of the Bmi1 in colon cancer and its relevance to other characteristics, especially the 5-year survival of colon cancer. The expression of Bmi1 was examined in colorectal carcinoma (n = 98) by using real-time polymerase chain reaction. Expression was correlated with clinicopathologic variables, 5-year overall survival (OS) rates. We for the first time found that high expression of Bmi1 was significantly associated with poor survival. Fourfold Table Chi-square Test analysis revealed that Bmi1 expression was closely related to TNM stage and histologic grade, while not relevant to age. In summary, the high expression of polycomb-group protein Bmi1 is an essential and important predictor of colorectal cancer prognosis.

Correlation of F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value and EGFR mutations in advanced lung adenocarcinoma.

Abstract: Objective Epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma are involved in the tumorigenesis and regulation of cell metabolism via Akt signaling. F-18 fluorodeoxyglucose-positron emission tomography ([18F]FDG PET), a functional imaging modality, can be used to measure tumor cell metabolism. Thus, in this study, we hypothesize that there exist correlations between EGFR mutation status and [18F]FDG uptake of advanced lung adenocarcinoma. Methods From May 2004 to April 2008, patients with stage IIIB or IV lung adenocarcinoma who underwent [18F]FDG PET and EGFR mutation analysis before receiving any treatment were eligible to participate in this study. The association of EGFR mutation status with patient characteristics and the SUVMAX from the [18F]FDG PET was evaluated. Multivariate logistic regression analysis was used to analyze predictors of EGFR mutations. Results Seventy-seven lung adenocarcinoma patients were included in this study. EGFR mutations were identified in 49 (64%) of the patients. The [18F]FDG uptake was significantly higher in EGFR-mutant (mean SUVMAX = 10.5 ± 4.7) than wild-type (8.0 ± 3.3) lung adenocarcinoma patients (P = 0.008). The median SUVMAX was 9.5, and patients with an SUVMAX ≥ 9.5 were more likely to harbor EGFR mutations (P = 0.009). In the multivariate analysis, an SUVMAX ≥ 9.5 remained a statistically significant predictor of EGFR mutations (P = 0.005). Conclusions Among Asian patients with advanced lung adenocarcinoma, those with higher SUVMAX on the [18F]FDG PET are more likely to carry EGFR mutations.

A systematic review of FDG-PET in breast cancer.

Abstract: Objetive To assess the safety and efficacy of FDG-PET in breast cancer in the diagnostic of primary tumours, lymph node staging, the detection of recurrent disease/metastases, and the assessment of chemotherapy treatment. Methods A systematic review was undertaken. A search was made for primary studies, other systematic reviews, and health technology assessment reports in different databases. Results A total of 73 reports were included. FDG-PET does not appear to be sufficiently accurate to be used in isolation for ruling out the presence of a primary tumour. In lymph gland staging, FDG-PET does not appear to be accurate enough to detect occult axillary metastases or micrometastases (sensitivity 20 and 50%, respectively); sentinel node biopsy is required for confirmation. In the detection of bone metastases, FDG-PET should be complemented with other tests such as bone gammagraphy or SPECT. The assessment of response to chemotherapy, there seems to be no uniform criterion for establishing a standardized uptake value (SUV) for FDG that would allow responders and non-responders to be distinguished. Conclusions FDG-PET is insufficiently sensitive to rule out small primary tumours. Due to the high number of false positives returned, it cannot replace axillary dissection in axillary lymph gland staging. A complete biochemical response identified by FDG-PET should not be relied upon to mean an absence of disease since the technique cannot detect residual microscopic elements.

Protective effects of propolis and related polyphenolic/flavonoid compounds against toxicity induced by irinotecan

Abstract: Despite the excellent chemotherapeutic effect of irinotecan, its cytotoxicity and genotoxicity in normal cells remains a major problem in chemotherapy. This study was carried out to find whether propolis preparations and related flavonoids (quercetin, naringin) might enhance irinotecan-induced cytotoxicity to tumor cells in mice bearing Ehrlich ascites tumors (EAT) while protecting normal blood, liver, and kidney cells. The preparation of propolis and their flavonoids were given to mice intraperitoneally at a dose of 100 mg kg−1 body weight for three consecutive days before the ip injection of EAT cells (2 × 106). Irinotecan was administered ip at dose of 50 mg kg−1 on days 3, 4, and 5 after tumor cell inoculation. The combination treatment resulted in substantial inhibition of the growth of EAT cells as well as treatment with quercetin or irinotecan alone, whereas other treatment by itself showed little effect. However, when mice were pre-treated with test components prior to irinotecan, the frequencies of irinotecan-induced micronuclei (MN) was decreased but in mice bearing tumor QU and EEP increased number of micronucleated cells. Propolis preparation and related flavonoids were found to exhibit an important immunomodulatory effect and could decrease irinotecan-induced toxic and genotoxic effects to normal cells without effecting irinotecan cytotoxicity in EAT cells.

Survival and prognostic factors in small cell lung cancer.

Abstract: The purposes of this study were to evaluate the treatment outcome of patients with small cell lung cancer (SCLC), focusing on the prognostic factors for response to therapy and overall survival. A retrospective analysis was performed on 116 consecutive patients with SCLC diagnosed from January 1997 to December 2005. Collected data included demographic information, pretreatment clinical assessment, treatment regimen, and outcome information. Prognostic factors were analyzed by log-rank test and Cox regression model. Results showed that performance status (PS) 0-1, limited disease, normal serum carcinoembryonic antigen (CEA), and vascular endothelial growth factor (VEGF) level were associated with improved response rate. The univariate analysis showed that sex, disease extent, PS, serum CEA, and VEGF level significantly influenced overall survival. In multivariate analysis, disease extent, PS, serum CEA, and VEGF level were identified as independent prognostic factors. In addition, prophylactic cranial irradiation (PCI) and number of metastatic sites were independent prognostic factors in limited disease and extensive disease, respectively. We concluded that disease extent, PS, serum CEA, and VEGF level are strong predictors of both response and survival. Female sex was a favorable prognostic factor for survival. Moreover, the prognostic factors for limited disease were good PS, normal serum CEA and VEGF level, and PCI, the prognostic factors for extensive disease were good PS, one metastatic site, normal serum CEA, and VEGF level. The identification of prognostic factors may be useful for the better evaluation of treatment outcome in clinical trials and the use of a targeted and specific treatment.

Clinical utility of circulating matrix metalloproteinase-7 (MMP-7), CC chemokine ligand 18 (CCL18) and CC chemokine ligand 11 (CCL11) as markers for diagnosis of epithelial ovarian cancer.

Abstract: Ovarian cancer remains a highly lethal disease The aim of the present study was to evaluate the usefulness of measuring serum matrix metalloproteinase-7 (MMP-7), CC chemokine ligand 18 (CCL18) and CC chemokine ligand 11 (CCL11) in comparison with serum cancer antigen 125 (CA 125) for diagnosis of epithelial ovarian cancer (EOC) This study included 51 patients with EOC, 27 patients with benign ovarian lesions and 29 healthy volunteers Serum CA 125 was determined by microparticle enzyme immunoassay, while serum MMP-7, CCL18 and CCL11 were measured using enzyme-linked immunosorbent assay The sensitivity and specificity were 863% and 929% for CA 125, 804% and 875% for MMP-7, 843% and 911% for CCL18 and, 686% and 625% for CCL11 Combination of CA 125, MMP-7, CCL18 and CCL11 gave a promising sensitivity of 100%, but specificity was decreased to 607% The combined use of serum CA 125, MMP-7, CCL18 and CCL11 effectively detected early stages EOC with high sensitivity of 944% Our data indicate that serum MMP-7, CCL18 and CCL11, in combination with CA 125 could be useful in diagnosis of EOC

Imatinib mesylate-induced acute liver failure in a patient with gastrointestinal stromal tumors.

Abstract: Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia, Philadelphia-positive acute lymphoblastic leukemia, and advanced gastrointestinal stromal tumors. Several cases of hepatotoxicity, including fatal liver failure, have been reported with the long-term use of imatinib mesylate. Generally hepatotoxicity resolves after discontinuation of imatinib. Despite discontinuation of imatinib, hepatotoxicity can be progressive. Steroid may be useful in these patients and should be started early. We report a 53-year-old woman with advanced gastrointestinal stromal tumors who developed hepatotoxicity while receiving imatinib and subsequently acute liver failure. Ten weeks after commencing imatinib treatment, hepatotoxicity was determined. Imatinib was immediately ceased. Subsequently, a week later hepatic encephalopathy, jaundice, and coagulopathy occurred. Prednisolone was commenced. Liver biopsy was performed five weeks after the determining of hepatotoxicity. Biopsy showed sinusoidal congestion, necrosis of hepatocytes, inflammation, and hepatocyte drop out around the hepatic venule consistent with drug toxicity. Her liver function tests normalized with a nine-week prednisolone treatment. The patient was discharged. Her liver enzymes remained in normal range following visits. In cases of imatinib-induced acute hepatitis, the administration of prednisolone may be useful in the resolution of the acute episode and allow the reintroduction of a drug without risking recurrence of hepatitis.

Immunohistochemical analysis revealed CD34 and Ki67 protein expression as significant prognostic factors in colorectal cancer

Abstract: CD34, cytokeratin (CK) 19, cytokeratin (CK) 20, and Ki67 have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD34, CK19, CK20, and Ki67 expressions in colorectal cancer (CRC) and to evaluate their involvement in the progression of CRC. CD34, CK19, CK20, and Ki67 expressions were assessed in paraffin-embedded specimens collected from 152 cases of CRC and 30 paired normal colorectal tissues by immunohistochemistry. The relationships between CD34, CK19, CK20, and Ki67 expressions and CRC were evaluated. The association of CD34 and Ki67 protein expressions with the clinicopathological characteristics and the prognosis of CRC were subsequently assessed. CD34, CK19, CK20, and Ki67 expressed highly in CRC tissues relative to normal colorectal tissues. Using immunostaining scoring, a significant correlation of CD34 and Ki67 with the UICC staging and histo-differentiation of CRC was found (P 0.05). Meanwhile, no relationship of CD34, CK19, CK20, and Ki67 with the location of CRC was found (P > 0.05). Patients with high expressions of CD34 and Ki67 had the lowest survival (P < 0.05). The results suggest that concurrent expression of CD34 and Ki67 may be an important characteristic of CRC which may help in the prediction of CRC progression.

Characteristics and quality of life analysis of caregivers of cancer patients

Abstract: Cancer affects not only the individuals with cancer, but also their families considerably. The aim of this study was to determine the sociodemographic characteristics and home care needs of caregivers of cancer patients receiving chemotherapy and evaluate their quality of life scores. A total of 126 primary caregivers of patients receiving chemotherapy who were eligible for inclusion criteria participated in the study. Data were collected using a questionnaire that included sociodemographic questions for both patients and caregivers and the World Health Organization Quality of Life-Short Form, Turkish Version (WHOQOL-BREF(TR)) for the caregivers. The mean domain scores of WHOQOL-BREF(TR) were 15.3 ± 2.8 for physical, 14.6 ± 2.8 for psychological, 14.4 ± 3.3 for social, 13.7 ± 2.8 for environment, and 14 ± 2.5 for national environment domains. Caregivers were, on average, younger than the patients and the mean age of the caregivers was 45 years. Around 70% of caregivers were living with the patients, 60.3% of caregivers shared the care-giving process with someone else, and his/her children supported in care-giving activities in 20.6%. According to caregivers, patients needed assistance for one or more daily living activities. Caregivers’ higher age, unemployment status, female gender, low education level, their own diagnosed health problems, care duration above 18 months, and having difficulties to continue social activities had negative effects on their quality of life. Cancer patients’ families are also affected from cancer. We may suggest that including caregivers in the context of home care and universalizing home care programs can reduce caregivers’ burden.

A retrospective study of unicentric and multicentric Castleman’s disease: a report of 52 patients

Abstract: Castleman’s disease (CD) is a rare disorder characterized by non-cancerous tumor growth that may develop in the lymph node tissue at a single site or throughout the body (Castleman et al. in Cancer 9:822–830, 1956). It involves hyperproliferation of specific B cells that produce the cytokine IL-6. This disorder is often undiagnosed or misdiagnosed. For this reason, only very few patients have been reported, and little information is available in the literature. In hopes of providing a better understanding of this rare disease, this report examines 52 patients with Unicentric Castleman’s disease (UCD) and Multicentric Castleman’s disease (MCD) treated from 1999–2008 at a single institution. Fifty-two patients with CD, along with their histological diagnoses, were collected. Patients were divided into two groups—the more common UCD and the less common MCD. Relevant clinical, pathological, and laboratory data were examined in order to evaluate treatment responses, with symptom onsets and survival period serving as the endpoints of the assessment. Each of the 48 patients with UCD exhibited benign symptoms and underwent a curative surgical resection with excellent prognosis. All of the four patients with MCD received surgical resection. Three of the four patients relapsed and received radiotherapy and/or chemotherapy. Only one of the three post-treatment patients survived. UCD is manifested in the form of benign, painless, slow lymph node enlargement that is generally asymptomatic. Complete surgical removal is recommended as a course of curative treatment. The multicentric form of CD exhibits a progressive clinical course with potential for malignancy. There is currently no standard therapy for MCD.

Platelet count: association with prognosis in lung cancer

Abstract: Lung cancer (LC) is now the leading cause of cancer mortality in the world, therefore it would be useful to identify prognostic factors to determine patient outcome. The objective of this study is to evaluate the usefulness of platelet counts at the time of diagnosis as a prognostic factor. A retrospective study of patients with histological diagnostic evidence of LC was carried in our catchment area over a 3-year period. Survival adjusted for other factors was assessed according to the platelet count at the time of diagnosis. Patients with platelet levels within the reference range (RR) (135000–381000/µl) were divided into two groups, between 135000–258000/µl and 258000–381000/µl. A third group was made up of patients with platelet counts over 381000/µl. Adjusted survival was analysed using Cox regression models. Patients with high platelets have a 37% worse survival than those with a platelet level within the RR, but lower than 258000/µl. When tumour stage is included in the covariates, platelet levels are no longer an independent survival factor. In conclusion, platelet levels at the time of diagnosis could be a useful prognostic factor in LC.

High-resolution melting analysis of ADAMTS18 methylation levels in gastric, colorectal and pancreatic cancers

Abstract: A disintegrin and metalloprotease with trombospondin motifs (ADAMTS) is a family of proteins characterized by the presence of a metalloproteinase domain linked to a variety of specialized ancillary domains. ADAMTS18 is a putative tumor suppressive gene related to nasopharyngeal carcinoma. We used high-resolution melting (HRM) analysis to detect the methylation levels of ADAMTS18 gene in 100 gastric cancers, 100 colorectal cancers, 70 pancreatic cancers, and equal number of adjacent normal tissues. The frequency of ADAMTS18 methylation in all three types of cancers was significantly higher than that in normal tissues. Expression levels of ADAMTS18 were inversely correlated with methylation levels. No significant association was found between ADAMTS18 methylation status and TNM staging in the cancers. In summary, epigenetic regulation of ADAMTS18 was associated with carcinogenesis. The application of HRM analysis is a fast and high-throughput way to investigate the epigenetic status of ADAMTS18.