Is DCIS Cancer?

2nd Wednesday, 2015  |   Breast Cancer, Cancer  |  no comments

samopregled-300x200   As many as 60,000 American women each year are told they have a very early stage of breast cancer — Stage 0, as it is commonly known — a possible precursor to what could be a deadly tumor. And almost every one of the women has either a lumpectomy or a mastectomy, and often a double mastectomy, removing a healthy breast as well. Yet it now appears that treatment may make no difference in their outcomes. Patients with this condition had close to the same likelihood of dying of breast cancer as women in the general population, and the few who died did so despite treatment, not for lack of it, researchers reported Thursday in JAMA Oncology. continue reading

Gambogenic acid

29th Wednesday, 2015  |   Breast Cancer, Cancer, Lung Cancer  |  no comments

Cancer: Breast
Action: Overcomes MDR, Adriamycin
Adriamycin (ADR) is beneficial for the treatment of breast cancer. However, its wide application often leads to drug resistance in clinic practice, which results in treatment failure. Gambogenic acid (GNA), a polyprenylated xanthone isolated from the traditional medicine gamboge, has been reported to effectively inhibit the survival and proliferation of cancer cells.
An MTT assay was used to evaluate the inhibitory effect of the drugs on the growth of MCF-7 and MCF-7/ADR cell lines. The effects of drugs on apoptosis were detected using Annexin-V APC/7-AAD double staining. The expression of apoptosis-related proteins and the proteins in the PTEN/PI3K/AKT pathway were evaluated by Western blot analysis.
In the MCF-7/ADR cell lines, the IC50 (half maximal inhibitory concentration) of the group that received combined treatment with GNA and ADR was significantly lower than that in the ADR group, and this value decreased with an increasing concentration of GNA. In parallel, GNA treatment increased the chemosensitivity of breast cancer cells to ADR. T
The study by He et al., (2015) has indicated a potential role for GNA to increase the chemosensitivity of breast cancer cells to ADR. This modulatory role was mediated by suppression of the PTEN/PI3K/AKT pathway that led to apoptosis in MCF-7/ADR cells. This work suggests that GNA may be used as a regulatory agent for treating ADR resistance in breast cancer patients.
He Y, Ding J, Lin Y, et al. Gambogenic acid alters chemosensitivity of breast cancer cells to Adriamycin. BMC Complementary and Alternative Medicine 2015, 15:181 doi:10.1186/s12906-015-0710-8


Cancer: Lung
Action: Autophagy
Gambogenic acid (GNA) is one of the active compounds of Gamboge, a traditional medicine that was used as a drastic purgative, emetic, or vermifuge for treating tapeworm. Recently, increasing evidence has indicated that GNA exerts promising anti-tumor effects. In the present paper, Mei et al., (2014) found that GNA could induce the formation of vacuoles, which was linked with autophagy in A549 and HeLa cells. Further studies revealed that GNA triggers the initiation of autophagy based on the results of MDC staining, AO staining, accumulation of LC3 II, activation of Beclin 1 and phosphorylation of P70S6K. Similar results were obtained using a xenograft model. Their findings show, for the first time, that GNA can cause aberrant autophagy to induce cell death and may suggest the potential application of GNA as a tool or viable drug in anticancer therapies.
Mei W, Dong C, Hui C, Bin L, Fenggen Y, Jingjing S, et al. (2014) Gambogenic Acid Kills Lung Cancer Cells through Aberrant Autophagy. PLoS ONE 9(1): e83604. doi:10.1371/journal.pone.0083604


Cancer: Triple Negative Breast
Action: Decrease bcl-2, inhibited cell proliferation, apoptosis
Zhou et al., (2013) used nude mouse models to detect the effect of gambogenic acid on breast tumors, analyzing expression of apoptosis-related proteins in vivo by Western blotting. Effects on cell proliferation, apoptosis and apoptosis-related proteins in MDA-MB-231 cells were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase-3,-8,-9 were also used to detect effects on caspase family members.
They found that gambogenic acid suppressed breast tumor growth in vivo, in association with increased expression of Fas and cleaved caspase-3,-8,-9 and bax, as well as decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell proliferation and induced cell apoptosis in a concentration-dependent manner.
Gambogenic acid suppressed breast cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor and mitochondrial pathways in vivo and in vitro.
Zhou J, Luo YH, Wang JR, Lu BB, Wang KM, Tian Y. Gambogenic acid induction of apoptosis in a breast cancer cell line. Asian Pac J Cancer Prev. 2013;14(12):7601-5.

Potential Role of Ginseng in the Treatment of Colorectal Cancer

17th Wednesday, 2015  |   Colorectal Cancer, Colorectal Cancer  |  no comments

Colorectal cancer remains one of the most prevalent cancer and a leading cause of cancer related death in the US. Many currently used chemotherapeutic agents are derived from botanicals. Identifying herbal sources, including those from ginseng family, to develop better anti-cancer therapies remains an essential step in advancing the treatment of the cancer. In this article, potential roles of ginseng herbs, especially American ginseng and notoginseng, in colorectal cancer therapeutics are presented. The major pharmacologically active constituents of ginsengs are ginsenosides, which can be mainly classified as protopanaxadiol and protopanaxatriol groups. Structure-activity relationship between their chemical structures and pharmacological activities are discussed.

In addition, various steaming temperature and time treatment of the ginseng herbs can change ginsenoside profiles, and enhance their anti-cancer activities. This heat treatment process may increase the role of ginseng in treating colorectal cancer.

Wang C-Z, Yuan C-S. Am. J. Chin. Med. 36, 1019 (2008). DOI: 10.1142/S0192415X08006545

Melanoma and chronic inflammatory patterns

26th Tuesday, 2015  |   Uncategorized  |  no comments

proj13afig1 Inflammasome: activation mechanisms Inflammation is a rapid biologic response of the immune system in vascular tissues, directed to eliminate stimuli capable of causing damage and begin the process of repair. The macromolecular complexes known as “inflammasomes” are formed by a receptor, either NOD (NLR) or ALR, the receptor absent in melanoma 2 (AIM2). In addition, the inflammasome is formed by the speck-like protein associated to apoptosis (ASC) and procaspase-1, that may be activated by variations in the ionic and intracellular and extracellular ATP concentrations; and the loss of stabilization of the fagolisosomme by internalization of insoluble crystals and redox mechanisms. As a result, there is activation of the molecular platform and the processing of inflammatory prointerleukins to their active forms. There are two modalities of activation of the inflammasome: canonical and non-canonical, both capable of generating effector responses. Recent data associate NLRP 3, IL-1? and IL-18 in the pathogenesis of a variety of diseases, including atherosclerosis, type II diabetes, hyperhomocysteinemia, gout, malaria and hypertension. The inflammasome cascade is emerging as a new chemotherapeutic target in these diseases. In this review we shall discuss the mechanisms of activation and regulation of the inflammasome that stimulate, modulate and resolve inflammation. Source Suárez R, Buelvas N. Invest Clin. 2015 Mar;56(1):74-99. C-reactive protein as a marker of melanoma progression. Two independent sets of plasma samples from a total of 1,144 patients with melanoma (587 initial and 557 confirmatory) were available for CRP determination. Kaplan-Meier method and Cox regression were used to evaluate the relationship between CRP and clinical outcome. Among 115 patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in CRP using nonparametric tests. Elevated CRP level was associated with poorer OS and MSS in the initial, confirmatory, and combined data sets (combined data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI, 1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after multivariable adjustment. As compared with CRP < 10 mg/L, CRP ? 10 mg/L conferred poorer OS in patients with any-stage, stage I/II, or stage III/IV disease and poorer disease-free survival in those with stage I/II disease. In patients who underwent sequential evaluation of CRP, an association was identified between an increase in CRP and melanoma disease progression. CONCLUSION: CRP is an independent prognostic marker in patients with melanoma. CRP measurement should be considered for incorporation into prospective studies of outcome in patients with melanoma and clinical trials of systemic therapies for those with melanoma. Source Fang S, Wang Y, Sui D, et al. J Clin Oncol. 2015 Apr 20;33(12):1389-96. doi: 10.1200/JCO.2014.58.0209. Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling. Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients’ progression-free and overall survival. CONCLUSION: SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment. Source Findeisen P, Zapatka M, Peccerella T, et al. J Clin Oncol. 2009 May 1;27(13):2199-208. doi: 10.1200/JCO.2008.18.0554.

Circadian Responses to Chemo

27th Monday, 2015  |   Uncategorized  |  no comments

The Scientist 21 April 2015 After exposure to curcumin, rat cancer

cell populations undergo a daily cycle of cell death. Like tissues throughout the body, tumors may also keep time, and a few studies have suggested that responses to cancer therapies may be stronger at particular times during the day. Related to this idea of “chronotherapy,” scientists presented unpublished data at the American Association for Cancer Research (AACR) meeting in Philadelphia showing that the effect of curcumin on rat glioblastoma cells cycles according to a circadian rhythm. Curcumin, a component of the spice turmeric, is known to have anti-cancer properties, and researchers are testing it out as a potential therapeutic agent. Given that curcumin can activate a gene important to regulating the circadian clock, Ashapurna Sarma, a graduate student in Michael Geusz’s lab at Bowling Green State University, along with colleagues at the University of Findlay’s College of Pharmacy in Ohio, wanted to see whether the anti-tumor effects of curcumin display any circadian rhythms. The team exposed rat glioblastoma cells to curcumin and filmed them for five days via time-lapse microscopy. The researchers then went back through the images and at five-minute intervals, manually counted the cancer cells. They found that “there’s a lot more apoptosis” in the treated cells compared to controls, Sarma told The Scientist. And for one particular concentration of curcumin, treated cells peaked in die-offs just about every 24 hours. “Curcumin is most effective at inducing apoptosis of glioma cells at a specific phase of the circadian cycle,” the authors wrote in their AACR poster. Sarma said the findings could have implications as researchers working to develop curcumin as a therapy for cancer patients; perhaps tweaking the timing of treatment could optimize its efficacy.

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