Cancer Cell Int. 2008; 8: 9
One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells.,
Cancer Cell Int. 2008; 8: 9.
Primary malignant tumors such as high grade gliomas diffusely migrate into the brain early in the disease course, disseminating tumor microsatellites to distant regions of the central nervous system [4]. These tentacles of tumor exist interspersed between normal functional tissues. Complete surgical resection of many malignant brain tumors is not practical by virtue of their anatomical location and the relationship of this diffuse disease relative to eloquent functional tissue. Adjuvant therapies including chemotherapy and radiation therapy are often used in conjunction with surgery for many types of cancer to attempt eradication of the residual tumor [5],
Blood. 2006 March 1; 107(5): 2170–2179.
Hematopoietic stem cell (HSC) self-renewal is driven by both intrinsic and extrinsic factors, but the molecular mechanism specifying whether developmental potential is lost or retained during asymmetric cell divisions is unknown. Serial transplantation studies have clearly indicated that self-renewal potential of HSCs is impaired after replicative stress.1,2 HSC activity may be irreversibly lost in a single cell division,3,4 indicating that the epigenetic regulation of gene expression, largely dictated by the histone code, may play an important role. Recently, substantial attention has focused on the role of Polycomb group (PcG) proteins in stem cell self-renewal.,
Ann Gen Psychiatry. 2007; 6: 25.
The authors acknowledge the written consent for publication obtained from the patient featured in the manuscript.
PLoS Med. 2006 October; 3(10): e420.
Nuclear factor erythroid-2 related factor 2 (NRF2), a cap 'n' collar basic leucine zipper transcription factor, regulates a transcriptional program that maintains cellular redox homeostasis and protects cells from oxidative insult, including from chemotherapeutic agents [7–9]. NRF2 activates transcription of its target genes through binding specifically to the antioxidant response element (ARE) found in those gene promoters. The NRF2-regulated transcriptional program includes a broad spectrum of genes, including ones encoding antioxidants (e.g., γ-glutamyl cysteine synthetase modifier subunit [GCLm], γ-glutamyl cysteine synthetase catalytic subunit [GCLc], heme oxygenase-1, superoxide dismutase, glutathione reductase [GSR], glutathione peroxidase, thioredoxin, thioredoxin reductase, peroxiredoxins[PRDX], and cysteine/glutamate transporter [SLC7A11]) [7,8], xenobiotic metabolism enzymes (e.g., NADP[H] quinone oxidoreductase 1 [NQO1], GSTs, and UDP-glucuronosyltransferase) [7,8], and several ATP-dependent drug efflux pumps (e.g., MRP1 and MRP2) [10–12].
PLoS Med. 2006 October; 3(10): e420.
Cell Culture and ReagentsHBE4, NL20, A549, H460, H1435, H292, H23, H358, H1299, H1993, H1395, and H838 cells were purchased from American Type Culture Collection (Manassas, Virginia, United States) and cultured under recommended conditions. BEAS2B cells were provided by S. Reddy (Johns Hopkins University, Baltimore, Maryland, United States). All transfections were carried out using Lipofectamine 2000 (Invitrogen).
PLoS Med. 2006 October; 3(10): e420.
Figure 4 Status of KEAP1 and NRF2 Is Altered in Cancer Cells (A) Immunoblot showing increased nuclear localization of NRF2 in nuclear extracts (NE) from cancer cells. Cancer cells showed lower levels of KEAP1 (~69 kDa) and higher levels of NRF2 (~110 kDa) in total protein lysates (TP). NIVT and KIVT indicate NRF2 and KEAP1 in vitro transcribed/translated product, respectively. (B and C) Quantification of NRF2 and KEAP1 protein in immunoblots. For band densitometry, bands in nuclear extract blot (B) were normalized to Lamin B1, and those in total protein (C) were normalized to GAPDH. (D) Heat map showing relative expression of KEAP1, NRF2, and NRF2-dependent genes by real-time RT-PCR. Raw data for the heat maps are presented in Table S5.
PLoS Med. 2006 December; 3(12): e486.
Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The “rules” governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets.
PLoS Med. 2006 December; 3(12): e486.
Methods and FindingsIn an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5′ CpG islands, are induced from undetectable levels by 5-aza-2′-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors.
PLoS Med. 2006 December; 3(12): e486.
Quantitative RT-PCRExpression of LOX, NRCAM, BNC1, CCNA1, MAF, ALDH1A3, CTSZ, IRX4, MSX1, KLF11, SERPINB5, TKTL1, GAPDH, r18s, and CDKN2A was analyzed by quantitative real-time RT-PCR. Primers and probes were purchased from Applied Biosystems assay-on-demand, with the exception of p16, which was an assay-by-design (Hs00923893_m1) (http://www.appliedbiosystems.com). All samples were run on the Chromo 4 Real Time Detector (MJ Research [http://www.bio-rad.com]) twice, each time in duplicate. We averaged expression of GAPDH and r18s as internal reference genes to normalize input cDNA. Quantitative real-time reverse-transcriptase-PCR (QPCR) was performed in a reaction volume of 20 μl including 1 μl of cDNA. We used the comparative Ct method to compute relative expression values.
PLoS Med. 2006 December; 3(12): e486.
Figure 10 Histogram for Methylation Frequency of Indicated Genes in Prostate, Breast, Lung, and Colon Cancer and Companion Normal Tissue MSP data for indicated genes in breast (n = 14; red bars), lung (n = 20; black bars), prostate (n = 24; pale yellow bars), and colon (n = 24; grey bars) tumors and benign tissue (see Methods). Only samples with matching benign and tumor tissue are represented in the histogram. Gels were run and scored as above. SOX15 was omitted from this figure for clarity. Data for RASSF1A were obtained from [17,24,45,46]; data for p16 were obtained from [17,43,44,46].
PLoS Med. 2006 December; 3(12): e486.
We thank Dr. Juan Palazzo from Thomas Jefferson University for his kind gift of breast tumor DNAs; Jennifer Sayne in the UT Southwestern Tissue Procurement Core for obtaining prostate and colon DNA samples expeditiously; Shane Scoggin of the Simmons Cancer Center Genomics Core for working with us to optimize the amplification procedure for the microarrays; Anh Nguyen for working on the TA cloning; Drs. Elisabeth Martinez, Alexander Pertsemlidis, and Rolf Brekken for critical reading of the text.
Adv Urol. 2009; 2009: 341268.
Objective. It is to assess the feasibility, effectiveness, and safety of transobturator tension-free vaginal mesh (Prolift) and concomitant tension-free vaginal tape-obturator (TVT-O) system as a treatment of female anterior vaginal wall prolapse associated with stress urinary incontinence (SUI).
Adv Urol. 2009; 2009: 341268.
Methods. Between December 2006 and July 2007, 20 patients with anterior genital prolapse and voiding dysfunction were treated with the transobturator tension-free vaginal mesh (Prolift) and concomitant tension-free vaginal tape-obturator (TVT-O). Sixteen patients had stress urinary incontinence and 4 patients were considered at risk for development of de novo stress incontinence after the prolapse is repaired. All patients underwent a complete urodynamic assessment. All the patients underwent pelvic examination 4–6 weeks after the operation, and anatomical and functional outcomes were recorded.
Adv Urol. 2009; 2009: 341268.
Results. Twenty cystocoeles were repaired: 6 grade II, 12 grade III, and 2 grade IV. There were no vessel or bladder injuries. Eighteen patients had optimal anatomic results and 2 patients had persistent asymptomatic stage I prolapse.
