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Saturday, May 26, 2012

Free "Cancer" Journal supplement Issues from Wiley

A compound present in broccoli/broccoli sprouts can treat breast cancer

BREAKTHROUGH DISCOVERY






Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells





In the previous post I have mentioned about the Breast cancer stem cells which are more tumorigenic than normal  differentiated breast cancer cells. These stem cells are dangerous and controlling them is very important for cancer prevention. In a breakthrough discovery, Scientists from University of Michigan have identified compounds that can inhibit the breast cancer stem cells. Sulforaphane a compound found in broccoli/broccoli sprouts  Sulforaphane inhibits breast CSCs and downregulates the Wnt/beta-catenin self-renewal pathway. These findings support the use of sulforaphane for the chemoprevention of breast cancer stem cells. Further clinical studies can result in a new drug for breast cancer.

[Click Here to Read the Original Article]

Friday, May 25, 2012

Is radiation the right treatment for breast cancer ?


BREAKING DISCOVERY:

 Radiation treatment converts a normal breast cancer  cells to breast cancer stem cells which are more tumorigenic 


Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells (BCSCs) able to regrow a tumor while their progeny lack this ability. Recently, several groups reported enrichment for BCSCs when breast cancers were subjected to classic anticancer treatment. However, the underlying mechanisms leading to this enrichment are incompletely understood. Using non-BCSCs sorted from patient samples, we found that ionizing radiation reprogrammed differentiated breast cancer cells into induced BCSCs (iBCSCs). iBCSCs showed increased mammosphere formation, increased tumorigenicity, and expressed the same stemness-related genes as BCSCs from nonirradiated samples. Reprogramming occurred in a polyploid subpopulation of cells, coincided with re-expression of the transcription factors Oct4, sex determining region Y-box 2, Nanog, and Klf4, and could be partially prevented by Notch inhibition. We conclude that radiation may induce a BCSC phenotype in differentiated breast cancer cells and that this mechanism contributes to increased BCSC numbers seen after classic anticancer treatment.

Click here  Stem Cells2012;30:833–844 to read more

DNA CHIPS CAN BE USED FOR ASSESSING CHEMOTHERAPY SUCCESS - 2




This is the second post on use of gene expression profiling for assessing chemotherapy response or success. Here researchers from America and Korea have used  microRNA expression  profiling to identify specific signatures associated with clinical resistance to cisplatin/fluorouracil (CF) chemotherapy for gastric cancer. Biopsy samples were collected prior to chemotherapy from 90 gastric cancer patients treated with CF and from 34 healthy volunteers. At the time of disease progression, post-treatment samples were additionally collected from 8 clinical responders. miRNA expression was determined using a custom-designed Agilent microarray.  A miRNA signature distinguishing gastric cancer from normal stomach epithelium was identified. 30 miRNAs were significantly inversely correlated with time to progression whereas 28 miRNAs were significantly positively correlated with time to progression of 82 cancer patients (P<0.05). Prominent among the upregulated miRNAs associated with chemosensitivity were miRNAs known to regulate apoptosis, including let-7g, miR-342, miR-16, miR-181, miR-1, and miR-34. When this 58-miRNA predictor was applied to a separate set of pre- and post-treatment tumor samples from the 8 clinical responders, all of the 8 pre-treatment samples were correctly predicted as low-risk, whereas samples from the post-treatment tumors that developed chemoresistance were predicted to be in the high-risk category by the 58 miRNA signature, suggesting that selection for the expression of these miRNAs occurred as chemoresistance arose.
In summary these researchers have  identified 1) a miRNA expression signature that distinguishes gastric cancer from normal stomach epithelium from healthy volunteers, and 2) a chemoreresistance miRNA expression signature that is correlated with time to progression after CF therapy.

[CLICK HERE TO READ THE ORIGINAL ARTICLE PUBLISHED IN BMC MEDICAL GENOMICS]

DNA CHIPS CAN BE USED FOR ASSESSING CHEMOTHERAPY SUCCESS



The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Canadian researchers have shown that DNA chip based gene expression profiling can be used for assessing the success of chemotherapy for breast cancer. They used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents. Based on expression profiling of  anthracycline and taxane based chemotherapy response target based expression indices that predict breast tumor response to these drugs were identified. These gene expression signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol.  This study shows that a practical method for assessing the success of chemotherapy can be developed using gene expression profiling.
(More explanation about  DNA chip, expression profiling etc will be added in future posts)