Tanshinone IIA induces growth inhibition and apoptosis in gastric cancer in vitro and in vivo

As a phytochemical derived from the roots of Salvia miltiorrhiza Bunge, Tanshinone?IIA has been reported to possess anti-inflammatory and antioxidant activity. Studies in breast, colon, prostate and lung cancer indicate that Tanshinone?IIA may exhibit a promising antitumor activity. However, systemic studies of the cytotoxic effects of Tanshinone?IIA on gastric cancer have not been described. The present study offers a comprehensive evaluation of the antitumor effects of Tanshinone?IIA in gastric cancer cells in?vitro and in a mouse xenograft model. Cell viability and apoptosis in?vitro were evaluated through the MTT assay and flow cytometry analysis. The results indicate that Tanshinone?IIA can induce gastric cancer cell growth inhibition and apoptosis in a time- and concentration-dependent manner. Furthermore, we investigated the mechanism of the apoptotic effects induced by Tanshinone?IIA. We found that Tanshinone?IIA can not only cause cell cycle arrest in the G2/M phase, but also trigger the intrinsic apoptotic signaling pathway. The results suggest that Tanshinone?IIA may serve as an effective adjunctive reagent in the treatment of gastric cancer.     

RES function and tumour take and tumour growth in the liver and in the kidney—An experimental study in rats

This experimental study in rats examines tumour take and growth after RES modulation in an organ rich in macrophages—the liver—vs. an organ poor in macrophages—the kidney. A control group of 16 rats had 1.0 × 10⁶ transplantable adenocarcinoma cells inoculated in the liver and the same number in the left kidney. They were compared with a RE-stimulated group of 16 rats treated i.v. with Zymosan (3 mg/100 g for 3 days) and a RE-depressed group of 16 rats treated with i.v. methylpalmitate (100 mg/100 g for 3 days) before tumour inoculation. Tumour size was measured on days 7 and 14. The animals were killed on day 14. Mortality was significantly higher in methylpalmitate-treated rats than in control groups. Tumour take in the kidney was not affected by RES stimulation or depression. In the liver, RES stimulation caused significantly less tumour take. Depression of RES with methylpalmitate did not increase tumour take or tumour growth in the liver, which was very high in the control group.     

Body Mass Index and its Change in Adulthood and Breast Cancer Risk in China

Objective: To investigate the association between the risk of breast cancer and body mass index (BMI) andits change in adulthood. Methods: A population-based case-control study was conducted in China from 2008to 2009. The study sample included 643 cases with pathologically-confirmed breast cancer and 590 controls.Information on adult height and weight at diagnosis, at five years before diagnosis, and at age 21 years wascollected by face-to-face interview using a structured questionnaire. Odds ratios (ORs) and 95% confidenceintervals (CIs) were obtained using unconditional logistic regression analyses. Results: There was an increasedrisk of breast cancer associated with overweight or obesity in adulthood in Chinese women. Compared with thewomen who never had overweight or obesity in their adulthood, the adjusted ORs of breast cancer were 1.99(1.42-2.79) for a BMI ≥25.0 at age 21 and just before diagnosis. This rose to 3.04 (1.18-7.86) if, in addition, BMI≥25.0 was also present five years before diagnosis. Conclusion: Weight gain throughout adulthood is associatedwith an increased risk of breast cancer in Chinese women.     

in Vitro and in Vivo Inhibitory Effects of α-Mangostin on Cholangiocarcinoma Cells and Allografts

We investigated the anti-cholangiocarcinoma effect of α-mangostin from Garcinia mangostana pericarp extract (GM) in a human cholangiocarcinoma (CCA) cell line and a hamster CCA allograft model. In vitro, human CCA cells were treated with GM at various concentrations and for different time periods; then cell-cycle arrest and apoptosis were evaluated using flow cytometry, and metastatic potential with wound healing assays. In vivo, hamster allografts were treated with GM, gemcitabine (positive control) and a placebo (negative control) for 1 month; tumor weight and volume were then determined. Histopathological features and immunostaining (CK19 and PCNA) characteristics were examined by microscopy. The present study found that α-mangostin could: inhibit CCA cell proliferation by inducing apoptosis through the mitochondrial pathway; induce G1 cell-cycle arrest; and inhibit metastasis. Moreover, α-mangostin could inhibit CCA growth, i.e. reduce tumor mass (weight and size) and alter CCA pathology, as evidenced by reduced positive staining for CK19 and PCNA. The present study thus suggested that α-mangostin is a promising anti-CCA compound whose ready availability in tropical countries might indicate use for prevention and treatment of CCA.     

‘GAP’ in radiotherapy services in Australia and New Zealand in 2009

Aim: In this study we estimated (a) the number of linear accelerators required in Australia and New Zealand to achieve a 52.3% treatment rate; (b) the ‘GAP’ between the actual and required number of linear accelerators; c) the number of persons not treated (PNT), premature deaths (PD) and years of life lost (YLL) as a result of the ‘GAP’; and (d) to review the actions being taken by health jurisdictions in Australia and in New Zealand to address the ‘GAP’ and reach the 52.3% treatment rate. Material and Methods: The actual number of fully staffed and operating linear accelerators (A) in Australian and New Zealand was obtained from a survey of radiotherapy facilities in December 2009. The required number of linear accelerators (R) was calculated from the projected cancer incidence figures for 2009 and was based on 1.6 linear accelerators being required per 1000 new cancer patients. The ‘GAP’ in Radiotherapy services (G) was R minus A. The maximum treatment capacity (MTC) was the ratio of A over R multiplied by 52.3%, assuming that all linear accelerators were operating at 100% capacity. As each linear accelerator can treat 331 new patients each year, the number of new cancer PNT is G × 331. The estimated 5-year survival benefit from radiotherapy is 16%, and the average survival for all patients receiving radiotherapy (radical and palliative) is 0.76 year. Hence, the number of PD attributed to the ‘GAP’ is PNT × 16%, and the YLL to cancer is PNT × 0.76. A literature search and local knowledge of health department Radiotherapy Plans in all jurisdictions were used to determine the action being taken to achieve a 52.3% treatment rate. Results: In 2009, the ‘GAP’ was 50 linear accelerators in Australia and the MTC was 38%, the same as it was in 1999, but there has been an increase in PNT each year from 7419 in 1999 to 16 550 in 2009, and PD each year increased from 1187 in 1999 to 2649 in 2009, and YLL each year increased from 5638 in 1999 to 12 585 in 2009. In New Zealand in 2009, the ‘GAP’ was nine linear accelerators and the MTC was 38%. An estimated 3310 persons did not receive radiotherapy in 2009 in New Zealand, and as a result, there were 523 PD and 2266 YLL. The review showed that new and replacement machines were being installed in all jurisdictions in Australia and in New Zealand. Only Victoria and Queensland have a Radiotherapy Plan beyond 2010, but both have underestimated the projected cancer incidence. Conclusion: Urgent action is needed by health departments and governments on both sides of the Tasman to improve access and equity to this essential cancer treatment. There is merit in the Baume Report recommendation of establishing a national body to oversee radiotherapy services in all jurisdictions in Australia. A similar central body should also be considered for New Zealand.     

Bullatacin — in vivo and in vitro experience in an ovarian cancer model

The cytotoxicity and antitumor effects of the acetogenin Bullatacin were evaluated in vitro in multiple ovarian cancer cell lines and in vivo in a murine ovarian teratocarcinoma (MOT) model in C3HeB/FeJ mice. The in vitro cytotoxicity of Bullatacin against four human ovarian epithelial tumor cell lines (OC-194, OC-222, OVCAR-3, and A-2780) was assessed in 48- and 72-h tetrazolium-dye (MTT) cytotoxicity assays. The percentage of cytotoxicity was determined on the basis of the mean optical density of the respective untreated cells and the dose effective against 50% of the cells (ED₅₀) was calculated for each cell line. In vivo experiments were performed on adult female C3HeB/FeJ mice, which were injected i.p. with 10⁵ MOT cells and varying amounts of Bullatacin given either in a single dose or in 5 subsequent doses over 72 h. All mice were observed for survival relative to that of the control groups, which were injected either with 10⁵ MOT cells with or without serial injections of vehicle or with vehicle only. All four epithelial ovarian cancer cell lines displayed sensitivity to Bullatacin. The relative cytotoxic effects were very heterogeneous, with the ED₅₀ value ranging between 10^–7 g/ml for OC-194 and 4 g/ml for the cisplatin-resistant cell line OVCAR-3 in a 72-h MTT cytotoxicity assay. All mice that had been injected i.p. with 10⁵ MOT cells and 1.4 mg/kg or more of Bullatacin died within the first 24 h after injection, whereas all mice that had received 600 g/kg of Bullatacin or less survived equally as long as the controls that had been injected with MOT only (21.1±0.9 days). Mice that had received Bullatacin at a dose ranging from 600 g/kg to 1.4 mg/kg either died during the 1st day postinjection or survived, but not longer than the MOT control group. Serial i.p. injections of Bullatacin again either led to death of the mice within 24–48 h of the last dose of Bullatacin or did not have any effect on the survival of the mice as compared with the respective control groups, which had been injected with the tumor and serial injections of vehicle (22.5±2.2 days). In summary, Bullatacin showed no effect on MOT-caused animal death in C3HeB/FeJ mice at nonlethal dose ranges, whether it was given as a single i.p. dose or serially over 72 h. In vitro, however, it proved to be a very potent cytotoxic agent in a variety of ovarian cancer cell lines. As compared with other chemotherapeutic agents, which we accept as having clinically important antitumor efficacy against ovarian cancer, such as cisplatin or carboplatin, Bullatacin demonstrated a very favorable ED_{50 in vitro}/LD_{50 in vivo} (the dose lethal to 50% of the mice) ratio.This work was supported by the Bertha Warshaver Rubin Research Fund and was presented at the 21st annual meeting of the Western Association of Gynecologic Oncologists, May 19–23, 1993, Santa Monica, California     

Patterns and trends in esophageal cancer mortality and incidence in Europe (1980–2011) and predictions to 2015

BackgroundOver the last few decades, esophageal cancer incidence and mortality trends varied substantially across Europe, with important differences between sexes and the two main histological subtypes, squamous cell carcinoma (ESCC) and adenocarcinoma (EAC).Patients and methodsTo monitor recent esophageal cancer mortality trends and to compute short-term predictions in the European Union (EU) and selected European countries, we analyzed data provided by the World Health Organization (WHO) for 1980–2011. We also analyzed incidence trends and relative weights of ESCC and EAC across Europe using data from Cancer Incidence in Five Continents.ResultsLong-term decreasing trends were observed for male esophageal cancer mortality in several southern and western European countries, whereas in central Europe mortality increased until the mid-1990s and started to stabilize or decline over the last years. In some eastern and northern countries, the rates were still increasing. Mortality among European women remained comparatively low and showed stable or decreasing trends in most countries. Between 2000–2004 and 2005–2009, esophageal cancer mortality declined by 7% (from 5.34 to 4.99/100 000) in EU men, and by 3% (from 1.12 to 1.09/100 000) in EU women. Predictions to 2015 show persistent declines in mortality rates for men in the EU overall, and stable rates for EU women, with rates for 2015 of 4.5/100 000 men (about 22 300 deaths) and 1.1/100 000 women (about 7400 deaths). In northern Europe, EAC is now the predominant histological type among men, while for European women ESCC is more common and corresponding rates are still increasing in several countries.Conclusion(s)The observed trends reflect the variations in alcohol drinking, tobacco smoking and overweight across European countries.     

Where do we stand? Research and policy issues concerning inequalities in health and in healthcare

There are signs that the seriousness of the challenge posed by social inequalities in health and in healthcare is filtering through to governments in an increasing number of countries. The problem includes a large, and in some cases widening, gap between the health of the rich and the poor within countries, coupled with serious social and economic inequalities across society in general. Healthcare reforms are posing further dilemmas in relation to equity. The first part of this paper outlines some of the latest evidence on the scale and nature of the problem and the key research questions selected for future study in the national research programmes set up on the subject. The second part considers unemployment and health in more detail, illustrating some of the policy issues which this raises. The last part focuses on practical strategies for the health sector to adopt to build a more equitable policy response.     

Differential effects of tumor–platelet interaction in vitro and in vivo in glioblastoma

An elevated platelet count is considered an independent predictor of short survival in glioblastoma and various other tumor entities. Prothrombotic activity of the tumor microcirculation resulting in platelet activation and release of cytokines from activated platelets has been suggested to play a role. This study was designed to analyze the effects of platelet-released cytokines on glioblastoma and endothelial cell proliferation and migration in vitro, and the influence of platelet count on glioblastoma growth and angiogenesis in vivo. In cultured human glioblastoma, umbilical cord and cerebral microvascular endothelial cells platelet-released cytokines significantly stimulated proliferation and migration as well as sprouting and formation of capillary-like structures. In vivo, glioblastoma cells were implanted in mice followed by platelet depletion starting 1 or 8 days later. Tumor volume, proliferative index, and vessel density analyzed 14 days after engraftment did not differ between animals with a normal and a low platelet count. Likewise, no effect of platelet depletion over 20 days upon the volume of intracerebrally growing tumors was observed in mice. Additionally, proliferative activity and vessel density determined in tumor samples from patients operated upon glioblastoma did not show any correlation with the patients’ preoperative platelet count. Thus, we conclude that distinct proliferation- and chemotaxis-stimulating effects of platelet-derived cytokines can be achieved in vitro, while the platelet count does not exert a major influence on tumor growth and tumor angiogenesis in GBM in vivo.     

Study on the Difference in Expression of VEGF and bFGF and their Receptors in Young and Postmenopausal Women with Breast Cancer

Objective To study the difference in expression of VEGF and bFGF and their receptors in young and postmenopausal women with breast cancer. Methods Immunohistochemical methods (SABC) were used to study the expression of VEGF, FLK-1, bFGF and FLG on paraffin-embedded sections from 40 cases of young and 30 cases of postmenopausal women with breast cancer, The relationship between axillary lymph node metastasis and the expression of the growth factors and their receptors was studied. Results The mean expression of VEGF and bFGF and the positive rate of axillary lymph nodes in the young group were higher than that in the postmenopausal group (P< 0.01 or P< 0.05 ); the mean values of VEGF, bFGF, FLK-1 and FLG in cases of axillary lymph node metastasis were higher in patients without axillary lymph node metastasis in each group (P< 0.05 orP< 0.01); there was a significant difference between the mean expression of VEGF, bFGF, FLK-1 and FLG in cases of stage 0 ∼II comparaed to cases of stage III∼IV (P< 0.05 or P< 0.01). Conclusion The tumor vasculature is directly related to the high breast cancer aggressiveness in young women, a characteristic that might be due to the high expression of VEGF and bFGF.     

The role and status of fuzheng in cancer prevention and treatment

Traditional Chinese medicine (TCM) treatment of cancer has a long history, and is an important part of cancer prevention and control in China. Fuzheng, also cal ed reinforcing healthy qi and supplementing the root, is the most funda-mental principle of TCM in cancer prevention and control. In recent decades, this treatment has been thoroughly studied and widely applied, and played a crucial role in cancer prevention and treatment. With regard to the treatment of malignant tumors, Chinese medicine is mainly used in the fol owing areas:improving symptoms, enhancing the quality of life, reducing postop-erative recurrence and metastasis, increasing ef icacy and decreasing toxicity together with radiotherapy and chemotherapy treatments, and to some extent prolonging the survival of advanced tumors.     

TGF-β signalling and its role in cancer progression and metastasis

The transforming growth factor-β (TGF-β) system signals via protein kinase receptors and SMAD mediators to regulate a large number of biological processes. Alterations of the TGF-β signalling pathway are implicated in human cancer. Prior to tumour initiation and early during progression, TGF-β acts as a tumour suppressor; however, at later stages, it is often a tumour promoter. Knowledge about the mechanisms involved in TGF-β signal transduction has allowed a better understanding of cancer progression, invasion, metastasis and epithelial-to-mesenchymal transition. Furthermore, several molecular targets with great potential in therapeutic interventions have been identified. This review discusses the TGF-β signalling pathway, its involvement in cancer and current therapeutic approaches.     

Expression and Significance of Coxsackie and Adenovirus Receptor in Renal-Cell Carcinoma

OBJECTIVE To investigate the expression of Coxsackie and Adenovirus receptor (CAR) in renal-cell carcinoma and the relationship of the CAR to the biological behavior of the carcinomas.METHODS The immunohistochemical SP method was used to detect the expression of Coxsaekie and Adenovirus receptor in 48 cases of renalcell carcinoma and in 12 cases of normal renal tissue 2 cm away from the tumor tissue.RESULTS The positive rates of CAR were 100% in 12 cases of para-tumcr normal renal tissue and 35.4% in 48 cases of renal-cell carcinoma respectively. The difference of CAR expression between them was significant (P＜0.05). The grades of the tumor were as follows: 22 in Grade Ⅰ, 17in Grade Ⅱ and 9 in Grade Ⅲ with the CAR positive rate being 54.5%,23.5% and 11.1%, respectively. There was a negative correlation between CAR expression and tumor grading (P＜0.05). In addition, the number of the cases in stages Ⅰ to ⅣV were 19, 13, 11 and 5 respectively, with the respective positive rates being 57.9%, 30.8%, 18.2% and 0.0%, i.e. there also was a negative relationship between CAR expression and the stage (P＜0.05).CONCLUSION CAR expression is down-regulated in renal-cell carcinoma compared with normal tissue. The level of CAR may be a sensitive predictor of differentiation, invasion and metastasis. Loss of CAR expression correlates with the invasive phenotype in our analysis of renal-cell carcinoma.     

Nucleolar organizers and mitotic conditions in endometrial hyperplasia and carcinomaĭ

The study deals with the levels of nucleolar organizers (NO) and mitotic conditions in 85 samples of the endometrium (proliferative stage of menstrual cycle--5; glandular hyperplasia--10; adenomatosis--15; atypical hyperplasia--25 and adenocarcinoma--25). These findings point to a significant increase in NO number in atypical hyperplasia and especially in adenocarcinoma. The latter showed an inverse correlation between the index under study and cell differentiation stage. Endometrial mitosis displayed a higher mitotic index, a larger fraction of pathological mitoses and cells passing through metaphase as well as a variety of pathological forms of karyokinesis. A high correlation between NO number and mitotic index was observed for different conditions of the endometrium.     

Incidence,survival, and mortality of cancer in children and young adolescents in Belgium and the Netherlands in 2004–2015: A comparative population-based study

International comparisons of cancer surveillance measures may provide insight into inequalities in registration practices, etiological factors, and treatment strategies. This study aimed to compare incidence, survival, and mortality of cancer in children and young adolescents between Belgium and the Netherlands. All children (0–14 years) and young adolescents (15–17 years) diagnosed with cancer between 2004 and 2015 were selected from the population-based cancer registries of Belgium (N = 4739) and the Netherlands (N = 7322). Differences in incidence and mortality were expressed as standardized rate ratios (SRR; BE/NL). Five-year observed survival was calculated using the Kaplan–Meier method. During 2004–2015, the overall cancer incidence among children and young adolescents was similar in both countries. Incidence of neuroblastoma was significantly higher in Belgian children (2010–2015: SRR = 1.3, 95% CI 1.0–1.6). Five-year survival of all malignant cancers was comparable in 2010–2015, exceeding 80% in both age groups. Remarkable differences in survival existed in children for malignant central nervous system (CNS) tumors in 2004–2009 (BE = 62%, NL = 45%), for acute myeloid leukemia (BE = 68%, NL = 78%) and rhabdomyosarcomas (BE = 60%, NL = 79%) in 2010–2015, and for neuroblastoma in both periods (2004–2009: BE = 76%, NL = 64%; 2010–2015: BE = 82%, NL = 64%). Overall cancer mortality in children decreased by approximately 3 percent-points annually in both countries, but was slightly lower in Belgium in 2004–2009 (SRR = 0.9, 95% CI 0.7–1.0). Despite differences for specific cancer types, overall cancer incidence, survival, and mortality were comparable between Dutch and Belgian children and young adolescents in 2010–2015. Variability in screening, diagnosis, and registration practices probably explains the observed differences in incidence and survival of neuroblastoma and malignant CNS tumors.