No improvement noted in overall or cause-specific survival for men presenting with metastatic prostate cancer over a 20-year period

3rd Tuesday, 2013  |   Prostate Cancer  |  no comments

The below report suggests survival rates have not improved and no consistent improvement in overall or disease-specific survival in PCa due to PSA screening. Remember elevated PSA is not an indication of cancer but a sign of inflammation or sexual activity. The on going opinion is that sex and ejaculations before the blood draw can cause the prostate to produce more PSA and therefore give a false positive.


No improvement noted in overall or cause-specific survival for men presenting with metastatic prostate cancer over a 20-year period

Prostate cancer mortality in the United States has declined by nearly 40% over the last 25 years. However, to the authors’ knowledge, the contribution of prostate-specific antigen (PSA) screening for the early detection of prostate cancer remains unclear and controversial. In the current study, the authors attempted to determine whether improvements in survival over time among patients with metastatic prostate cancer have contributed to the decline in mortality. 

Men aged ≥ 45 years who presented with de novo metastatic prostate cancer from 1988 to 2009 were identified within the California Cancer Registry. Overall survival and disease-specific survival were estimated using the Kaplan-Meier method. A multivariate analysis with Cox proportional hazards modeling was performed to adjust for different distributions of variables between groups.

A total of 19,336 men presented with de novo metastatic prostate cancer during the study period. On multivariate analysis, overall survival was found to be better for men diagnosed from 1988 through 1992 and 1993 through 1998 than for men diagnosed in the most recent era (hazards ratio, 0.78; 95% confidence interval, 0.72-0.85 [P < .001] and HR, 0.79; 95% confidence interval, 0.74-0.86 [P < .001]). There was no improvement in disease-specific survival observed when comparing the most contemporary men (those diagnosed between 2004 and 2009) with those diagnosed between 1988 and 1997.

In this analysis of men presenting with de novo metastatic prostate cancer, no consistent improvement in overall or disease-specific survival could be demonstrated over time. These data suggest that improvements in survival for patients with advanced disease have not contributed substantially to the observed drop in prostate cancer mortality over the PSA era and that stage migration secondary to PSA screening plays a more prominent role.


Wu , J.N., et al. Cancer (Nov 2013) DOI: 10.1002/cncr.28485


Adiposity, mediating biomarkers and risk of colon cancer

25th Monday, 2013  |   Uncategorized  |  no comments


Adiposity is a risk factor for colon cancer. Krasimira Aleksandrova et al., evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. They analyzed data from a prospective nested case–control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. 
BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37–57%) of the association in men and 50% (95% CI 40–65%) of the association in women. Similar results were observed for the associations with BMI in men. 
These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.
International Journal of Cancer. Volume 134, Issue 3, pages 612–621, 1 February 2014. DOI: 10.1002/ijc.28368

Obesity and colorectal cancer.
Epidemiological data suggest that obesity is associated with a 30-70% increased risk of colon cancer in men, whereas the association is less consistent in women. Similar trends exist for colorectal adenoma, although the risk appears lower. Visceral fat, or abdominal obesity, seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/m(2) increase in BMI confers additional risk (HR 1.03). Obesity might be associated with worse cancer outcomes, such as recurrence of the primary cancer or mortality. Several factors, including reduced sensitivity to antiangiogenic-therapeutic regimens, might explain these differences.
The underlying mechanisms linking obesity to CRC are still a matter of debate, but metabolic syndrome, insulin resistance and modifications in levels of adipocytokines seem to be of great importance. Other biological factors such as the gut microbiota or bile acids are emerging.
Gut. 2013 Jun;62(6):933-47. doi: 10.1136/gutjnl-2013-304701.

Obesity and physical inactivity have been increasingly linked to colorectal cancer, but a new study suggests that these risk factors are only important in about half of all cases.
The study, published online February 26 in Cancer Research, found that increased body weight and decreased levels of physical activity are only associated with an increased risk for colorectal cancer that tests negative for the biomarker CTNNB1. This subtype accounted for 54% of the cases tested.
For CTNNB1-positive colorectal cancer, which accounted for the remaining 46% of cases tested, no such association was found. It appears that these cancers are independent of those lifestyle factors, says senior author Shuji Ogino, MD, PhD, associate professor of pathology at the Dana-Farber Cancer Institute and associate professor of epidemiology at the Harvard School of Public Health in Boston, Massachusetts. If physicians are able to identify individuals who are prone to develop CTNNB1-negative cancer, then it would be possible to strongly recommend physical activity,” Dr. Ogino noted.
Obesity and physical inactivity are associated with a higher risk of CTNNB1-negative colorectal cancer but not with CTNNB1-positive cancer risk. Furthermore, it was suggested that energy balance and metabolism status exerts its effect in a specific carcinogenesis pathway that is less likely dependent on WNT/CTNNB1 activation.

Cancer Research. February 26, 2013; doi: 10.1158/0008-5472.CAN-12-2276 

Rhizoma corydalis and rhizoma curcumae

4th Monday, 2013  |   Others  |  no comments


Synergy analysis of anticancer agents is an important approach to determining the ratio and/or dose of drugs for clinical combination therapy. However, this method is rarely used to evaluate the composition of traditional Chinese medicine formulation. ‘Yanhusuo San’ (YHSS), which consists of yanhusuo (Rhizoma Corydalis) and Ezhu (Rhizoma Curcumae), has been an archaic Chinese medicine prescription since the Song dynasty (960-1279 AD). Gao et al., (2008) previously demonstrated that either yanhusuo or ezhu has strong anticancer effect. 

Herein, Gao et al., (2009) sought to determine the possible synergic effect between these two Chinese herbs. They measured the IC50 of each herb extract and both extracts at different ratios of doses by MTT assay. Isobologram and combination index (CI) analyses were used to evaluate the synergistic effect of yanhusuo and ezhu in different fixed ratios. Results indicated that a combination of two herbal extracts exhibits the strongest anticancer cell proliferation effect at the ratio of 3:2 (ezhu to yanhusuo; referred to as E3Y2). 

Using Boyden Chamber assay, flow cytometry, and fluorescence microscopy analysis, we found that E3Y2 could markedly reduce the cell invasion ability and induce cytochrome c release rather than single use, but E3Y2 could not influence the cell cycle distribution. When the levels of ERK1/2, p-ERK1/2 and p-Rb were determined by Western blot analysis, we found that the E3Y2 significantly suppresses the level of p-ERK. Thus, our studies provide a plausible molecular basis of the synergistic anti-tumor effect of ezhu and yanhusuo.

Gao JL, Shi JM, He K, et al. 2008 Yanhusuo extract inhibits metastasis of breast cancer cells by modulating mitogen-activated protein kinase signaling pathways. Oncol Rep. 2008 Oct;20(4):819-24.

Gao JL, He TC, Li YB, Wang YT. 2009 A traditional Chinese medicine formulation consisting of Rhizoma Corydalis and Rhizoma Curcumae exerts synergistic anti-tumor activity. Oncol Rep. 2009 Nov;22(5):1077-83.

Cortex moutan induces bladder cancer cell death via apoptosis and retards tumor growth in mouse bladders

29th Tuesday, 2013  |   Bladder Cancer  |  no comments

Source Lin M-Y, Lee Y-R, Chiang S–Y, et al. Complementary and Alternative Medicine. Volume 2013 (2013)   bladder-cancer     Cortex Moutan is the root bark of Paeonia suffruticosa Andr. It is the herbal medicine widely used in Traditional Chinese Medicine for the treatment of blood-heat and blood-stasis syndrome. Furthermore, it has been reported that Cortex Moutan has anticancer effect. In this study, the Cortex Moutan extract was evaluated in bladder cancer therapy in vitro and in vivo. Cortex Moutan extract reduces cell viability with IC50 between 1~2?mg/ml in bladder cancer cells, and it has lower cytotoxicity in normal urotheliums. It arrests cells in G1 and S phase and causes phosphatidylserine expression in the outside of cell membrane. It induces caspase-8 and caspase-3 activation and poly(ADP-ribose) polymerase degradation. The pan caspase inhibitor z-VAD-fmk reverses Cortex Moutan-induced cell death. Cortex Moutan also inhibits cell invasion activity in 5637 cells. In mouse orthotopic bladder cancer model, intravesical application of Cortex Moutan decreases the bladder tumor size without altering the blood biochemical parameters. In summary, these results demonstrate the antiproliferation and anti-invasion properties of Cortex Moutan in bladder cancer cells and its antibladder tumor effect in vivo. Cortex Moutan may provide an alternative therapeutic strategy for the intravesical therapy of superficial bladder cancer. Cortex Moutan (CM, root bark of Paeonia suffruticosa Andr.), named Mu Dan Pi in Chinese, is the herbal medicine widely used in Traditional Chinese Medicine (TCM). It tastes bitter and pungent. According to TCM theory, it belongs to the light cold-type medicine and has the function of heat-clearing, promoting blood circulation, removing blood stasis, cooling the blood, and reducing the deficient heat. In clinical regimen, CM is usually used to treat heat in the blood and blood stasis syndromes. It is used as an analgesic (Tatsumi et al., 2004), antispasmodic, antiaggregatory (Hirai, Terano & Hamazaki, 1983; Lin et al., 1999) and antioxidative agent (Yoshikawa et al., 2000). In other reports, CM itself or its major component has been shown to treat various disorders like diabetes (Lau et al., 2007), Alzheimer’s disease (Fujiwara et al., 2009; Zhou et al., 2011), arthritis (Kim et al., 2012), inflammation (Chou, 2003; Wu & Gu, 2009), sepsis, brain ischemia-reperfusion injury (Hsieh et al., 2006), HIV infection (Au et al., 2001), and herpes simplex virus infection (Hsiang et al., 2001). Recently, there are also some reports showing the anitumor activity of CM, including renal carcinoma (Wang et al., 2012), DLD-1 human colon cancer cells (Xing et al., 2010), and gastric cancer (Choi et al., 2012). In addition, one component of CM, paeoniflorin, was reported to have antitumor effect through apoptosis in lung cancer cells (Hung et al., 2008). Bladder cancer is a common malignancy worldwide (Parkin, 2008). More than 90% of bladder cancers are transitional cell carcinoma (TCC) in the histology, and it is classified into two groups in the pathogenesis: nonmuscle invasive and muscle invasive (Babjuk et al., 2011). There are two groups of intravesical therapeutic agents for bladder cancer therapy. Bacillus Calmette-Guérin (BCG) is the immunotherapeutic agent, and mitomycin C is one of the chemotherapeutic agents (Babjuk et al., 2011; Manoharan, 2011). Up to now, Bacillus Calmette-Guérin (BCG), a immunotherapeutic agent and mitomycin C is one of the chemotherapeutic agents, which provokes considerable and sometimes serious side effects, and the recurrence rate remains high in spite of intravesical chemotherapy. There is certainly place for improvement in bladder cancer therapy. Intravesical antitumor herbal medicine may provide an alternative pathway in the treatment of TCC. References: Au TK, T. Lam L, Ng TB, et al. A comparison of HIV-1 integrase inhibition by aqueous and methanol extracts of Chinese medicinal herbs. Life Sciences, vol. 68, no. 14, pp. 1687–1694, 2001. Babjuk M, Oosterlinck W, Sylvester R, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. European Urology, vol. 59, no. 6, pp. 997–1008, 2011. Choi HS, Seo HS, Kim JH, et al. Ethanol extract of Paeonia suffruticosa Andrews (PSE) induced AGS human gastric cancer cell apoptosis via fas-dependent apoptosis and MDM2-p53 pathways. Journal of Biomedical Science, vol. 19, no. 1, p. 82, 2012. Chou TC. Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia. British Journal of Pharmacology, vol. 139, no. 6, pp. 1146–1152, 2003. Fujiwara H, Tabuchi M, Yamaguchi T, et al. A traditional medicinal herb Paeonia suffruticosa and its active constituent 1,2,3,4,6-penta-O-galloyl-beta-d-glucopyranose have potent anti-aggregation effects on Alzheimer’s amyloid beta proteins in vitro and in vivo. Journal of Neurochemistry, vol. 109, no. 6, pp. 1648–1657, 2009. Hirai A, Terano T, Hamazaki T. Studies on the mechanism of antiaggregatory effect of Moutan Cortex. Thrombosis Research, vol. 31, no. 1, pp. 29–40, 1983. Hsiang CY, Hsieh CL, Wu SL, et al. Inhibitory effect of anti-pyretic and anti-inflammatory herbs on herpes simplex virus replication. American Journal of Chinese Medicine, vol. 29, no. 3-4, pp. 459–467, 2001. Hsieh CL, Cheng CY, T. Tsai TH, et al. Paeonol reduced cerebral infarction involving the superoxide anion and microglia activation in ischemia-reperfusion injured rats. Journal of Ethnopharmacology, vol. 106, no. 2, pp. 208–215, 2006. Hung JY, Yang CJ, Y. Tsai YM, Huang H, & Huang M. Antiproliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligand-mediated apoptotic pathway in human non-small cell lung cancer A549 cells. Clinical and Experimental Pharmacology and Physiology, vol. 35, no. 2, pp. 141–147, 2008. Kim HS, Kim A, Lee JM, et al. A mixture of Trachelospermi caulis and Moutan cortex radicis extracts suppresses collagen-induced arthritis in mice by inhibiting NF-?B and AP-1. Journal of Pharmacy and Pharmacology, vol. 64, no. 3, pp. 420–429, 2012. Lau CH, Chan CM, Chan YW, et al. Pharmacological investigations of the anti-diabetic effect of Cortex Moutan and its active component paeonol. Phytomedicine, vol. 14, no. 11, pp. 778–784, 2007. Lin HC, Ding HY, Ko FN, Teng C, Wu Y. Aggregation inhibitory activity of minor acetophenones from Paeonia species. Planta Medica, vol. 65, no. 7, pp. 595–599, 1999. Manoharan M.Intravesical therapy for urothelial carcinoma of the bladder. Indian Journal of Urology, vol. 27, no. 2, pp. 252–261, 2011. Parkin DM. The global burden of urinary bladder cancer. Scandinavian Journal of Urology and Nephrology, no. 218, pp. 12–20, 2008. Tatsumi S, Mabuchi T, Abe T, et al. Analgesic effect of extracts of Chinese medicinal herbs Moutan cortex and Coicis semen on neuropathic pain in mice. Neuroscience Letters, vol. 370, no. 2-3, pp. 130–134, 2004. Wang SC, Tang SW, Lam SH et al. Aqueous extract of Paeonia suffruticosa inhibits migration and metastasis of renal cell carcinoma cells via suppressing VEGFR-3 pathway. Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 409823, 9 pages, 2012. Wu M & Gu Z. Screening of bioactive compounds from Moutan Cortex and their anti-inflammatory activities in rat synoviocytes. Evidence-based Complementary and Alternative Medicine, vol. 6, no. 1, pp. 57–63, 2009. Xing G, Zhang Z, Liu J, Hu H, Sugiura N. Antitumor effect of extracts from moutan cortex on DLD-1 human colon cancer cells in vitro. Molecular Medicine Reports, vol. 3, no. 1, pp. 57–61, 2010. Yoshikawa M, Ohta T, Kawaguchi A, Matsuda H. Bioactive constituents of chinese natural medicines. V. Radical scavenging effect of Moutan Cortex. (1): absolute stereostructures of two monoterpenes, paeonisuffrone and paeonisuffral. Chemical and Pharmaceutical Bulletin, vol. 48, no. 9, pp. 1327–1331, 2000.

Zhou J, Zhou L, Hou D, Tang J, et al. Paeonol increases levels of cortical cytochrome oxidase and vascular actin and improves behavior in a rat model of Alzheimer’s disease. Brain Research, vol. 1388, pp. 141–147, 2011.


vimiento d ‘une fillette

26th Saturday, 2013  |   Uncategorized  |  no comments

Saint-Jean-sur-Richelieu Une fillette de 2 años pourrait avoir enlev par sa m lundi, Saint Jean sur Richelieu, un hecho savoir mardi soir La S du Qu avant d ‘qu annoncer’ policiers elles auraient toutes les deux Localis en R TCH ont fait ONU Appel T Llene retrouver María Zábranská, qui avait quitt sa r avec sa m lundi matin. Cette derni qui vit en R TCH n ‘est pas ingresos avec l’ enfant en soir et comme pr comme le voulait l ‘ordonnance de vanguardia.

Le p de María est sans nouvelles de sa fille depuis,canada goose jacka dam et il craint Que sa m AIT quitt le Canada avec elle.

descripciones selon les transmises par les Autorit María mesure 90 cm (2 pi 11 po), Elle a les cheveux ch boucl qui descendiente jusqu ‘aux les Bruns yeux. Lorsqu’ elle a quitt Saint Jean sur Richelieu, elle portait ONU chandail malva avec un dessin de chien, ONU manteau Brun FONC une tuque, ONU rosa caché COU, et des bottes bleues avec des lignes rosas. Elle s ‘Exprime en fran et peut dire quelques mots et TCH es en espagnol.

Quant sa m Marcela Zábranská, elle mesure 1 m 68 (5 pi po 6) et p environ 86 kg (190 Ib). Elle a les yeux bleus et les cheveux rubios lisses jusqu ‘aux elle portait de la ONU chandail noir sans manches, ONU manteau noir de marque ganso de Canadá, un sac dos noir et pourrait avoir ONU sofás saco de color turquesa. Elle parle le TCH et s’ Exprime linea espagnol avec acento de la ONU.

Les enqu du Service des enqu r de la S du Qu travaillent sur ce expediente en colaboración avec les policiers du Service de la policía de Saint Jean sur Richelieu.

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