Next Issue
Previous Issue

Table of Contents

Cancers, Volume 3, Issue 4 (December 2011), Pages 3714-4293

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-33
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle DNA Methylation and the HOXC6 Paradox in Prostate Cancer
Cancers 2011, 3(4), 3714-3725; doi:10.3390/cancers3043714
Received: 4 August 2011 / Revised: 8 September 2011 / Accepted: 22 September 2011 / Published: 27 September 2011
Cited by 9 | PDF Full-text (258 KB) | HTML Full-text | XML Full-text
Abstract
Overexpression of the classical homeobox transcription factor HOXC6 is frequent in prostate cancers and correlates with adverse clinical parameters. Since surprisingly many HOXC6 target genes are downregulated in prostate cancer, it has been posited that oncogenic effects of HOXC6 in prostate cancer [...] Read more.
Overexpression of the classical homeobox transcription factor HOXC6 is frequent in prostate cancers and correlates with adverse clinical parameters. Since surprisingly many HOXC6 target genes are downregulated in prostate cancer, it has been posited that oncogenic effects of HOXC6 in prostate cancer may be unmasked by concurrent epigenetic downregulation of target genes exerting tumor suppressive effects. To test this hypothesis, we have studied the expression of three HOXC6 target genes, CNTN1 (encoding a cell adhesion protein), DKK3 and WIF1 (encoding WNT growth factor antagonists) as well as DNA methylation of DKK3 and WIF1. HOXC6 upregulation and association with poor prognosis were confirmed in our tissue series. The three target genes were each significantly downregulated in cancer tissues and expression of each one correlated inversely with that of HOXC6. Cases with lower WIF1 expression showed significantly earlier recurrence (p = 0.021), whereas no statistical significance was reached for CNTN1 and DKK3. Hypermethylation of DKK3 or WIF1 gene promoters was observed in a subset of cancers with downregulated expression, but was often weak. Our data support the hypothesis that HOXC6 target genes exerting tumor-suppressive effects are epigenetically downregulated in prostate cancer, but DNA methylation appears to follow or bolster rather than to cause their transcriptional inactivation. Full article
(This article belongs to the Special Issue Prostate Cancer)
Open AccessArticle Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy
Cancers 2011, 3(4), 3726-3739; doi:10.3390/cancers3043726
Received: 13 September 2011 / Revised: 20 September 2011 / Accepted: 22 September 2011 / Published: 28 September 2011
Cited by 4 | PDF Full-text (1757 KB) | HTML Full-text | XML Full-text
Abstract
Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the [...] Read more.
Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163+ cells were significantly increased based on the pathological grade. CD163+ cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163+ cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4+ and CD8+ T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163+ TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC. Full article
(This article belongs to the Special Issue Exploring Inflammation in Cancers)
Open AccessArticle Inhibitory Effect of a γ-Tocopherol-Rich Mixture of Tocopherols on the Formation and Growth of LNCaP Prostate Tumors in Immunodeficient Mice
Cancers 2011, 3(4), 3762-3772; doi:10.3390/cancers3043762
Received: 25 July 2011 / Revised: 15 September 2011 / Accepted: 15 September 2011 / Published: 28 September 2011
Cited by 11 | PDF Full-text (262 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, we determined the effects of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) on the growth and apoptosis of cultured human prostate cancer LNCaP cells. We also determined the effects of dietary γ-TmT on the formation and growth of LNCaP [...] Read more.
In the present study, we determined the effects of a γ-tocopherol-rich mixture of tocopherols (γ-TmT) on the growth and apoptosis of cultured human prostate cancer LNCaP cells. We also determined the effects of dietary γ-TmT on the formation and growth of LNCaP tumors in immunodeficient mice. In the in vitro study, we found that the activity of γ-TmT was stronger than α-tocopherol for inhibiting the growth and stimulating apoptosis in LNCaP cells. In the animal study, treatment of severe combined immunodeficient (SCID) mice with dietary γ-TmT inhibited the formation and growth of LNCaP xenograft tumors in a dose-dependent manner. Mechanistic studies showed that g-TmT administration inhibited proliferation as reflected by decreased mitosis and stimulated apoptosis as reflected by increased caspase-3 (active form) expression in LNCaP tumors. In addition, dietary administration of g-TmT increased the levels of a-, γ- and δ- tocopherol in plasma, and increased levels of γ- and δ- tocopherol were also observed in the prostate and in tumors. The present study demonstrated that g-TmT had strong anticancer activity both in vitro and in vivo. Additional studies are needed to determine the potential preventive effect of g-TmT for prostate cancer in humans. Full article
(This article belongs to the Special Issue Prostate Cancer)
Open AccessArticle The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer
Cancers 2011, 3(4), 3824-3837; doi:10.3390/cancers3043824
Received: 5 August 2011 / Revised: 22 September 2011 / Accepted: 28 September 2011 / Published: 11 October 2011
PDF Full-text (1184 KB) | HTML Full-text | XML Full-text
Abstract
Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT2-) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT2 [...] Read more.
Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT2-) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT2-receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT2-receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT2-receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence. Full article
(This article belongs to the Special Issue Prostate Cancer)
Open AccessArticle Forced Expression of ZNF143 Restrains Cancer Cell Growth
Cancers 2011, 3(4), 3909-3920; doi:10.3390/cancers3043909
Received: 9 August 2011 / Revised: 10 October 2011 / Accepted: 12 October 2011 / Published: 19 October 2011
Cited by 7 | PDF Full-text (523 KB) | HTML Full-text | XML Full-text
Abstract
We previously reported that the transcription factor Zinc Finger Protein 143 (ZNF143) regulates the expression of genes associated with cell cycle and cell division, and that downregulation of ZNF143 induces cell cycle arrest at G2/M. To assess the function of ZNF143 expression [...] Read more.
We previously reported that the transcription factor Zinc Finger Protein 143 (ZNF143) regulates the expression of genes associated with cell cycle and cell division, and that downregulation of ZNF143 induces cell cycle arrest at G2/M. To assess the function of ZNF143 expression in the cell cycle, we established two cells with forced expression of ZNF143 derived from PC3 prostate cancer cell lines. These cell lines overexpress genes associated with cell cycle and cell division, such as polo-like kinase 1 (PLK1), aurora kinase B (AURKB) and some minichromosome maintenance complex components (MCM). However, the doubling time of cells with forced expression of ZNF143 was approximately twice as long as its control counterpart cell line. Analysis following serum starvation and re-seeding showed that PC3 cells were synchronized at G1 in the cell cycle. Also, ZNF143 expression fluctuated, and was at its lowest level in G2/M. However, PC3 cells with forced expression of ZNF143 synchronized at G2/M, and showed lack of cell cycle-dependent fluctuation of nuclear expression of MCM proteins. Furthermore, G2/M population of both cisplatin-resistant PCDP6 cells over-expressing ZNF143 (derived from PC3 cells) and cells with forced expression of ZNF143 was significantly higher than that of each counterpart, and the doubling time of PCDP6 cells is about 2.5 times longer than that of PC3 cells. These data suggested that fluctuations in ZNF143 expression are required both for gene expression associated with cell cycle and for cell division. Full article
(This article belongs to the Special Issue Prostate Cancer)
Open AccessArticle Helical Tomotherapy in Children and Adolescents: Dosimetric Comparisons, Opportunities and Issues
Cancers 2011, 3(4), 3972-3990; doi:10.3390/cancers3043972
Received: 13 September 2011 / Revised: 7 October 2011 / Accepted: 17 October 2011 / Published: 25 October 2011
Cited by 2 | PDF Full-text (709 KB) | HTML Full-text | XML Full-text
Abstract
Helical Tomotherapy (HT) is a highly conformal image-guided radiation technique, introduced into clinical routine in 2006 at the Centro di Riferimento Oncologico Aviano (Italy). With this new technology, intensity-modulated radiotherapy (IMRT) is delivered using a helicoidal method. Here we present our dosimetric [...] Read more.
Helical Tomotherapy (HT) is a highly conformal image-guided radiation technique, introduced into clinical routine in 2006 at the Centro di Riferimento Oncologico Aviano (Italy). With this new technology, intensity-modulated radiotherapy (IMRT) is delivered using a helicoidal method. Here we present our dosimetric experiences using HT in 100 children, adolescents and young adults treated from May 2006 to February 2011. The median age of the patients was 13 years (range 1–24). The most common treated site was the central nervous system (50; of these, 24 were craniospinal irradiations), followed by thorax (22), head and neck (10), abdomen and pelvis (11), and limbs (7). The use of HT was calculated in accordance to the target dose conformation, the target size and shape, the dose to critical organs adjacent to the target, simultaneous treatment of multiple targets, and re-irradiation. HT has demonstrated to improve target volume dose homogeneity and the sparing of critical structures, when compared to 3D Linac-based radiotherapy (RT). In standard cases this technique represented a comparable alternative to IMRT delivered with conventional linear accelerator. In certain cases (e.g., craniospinal and pleural treatments) only HT generated adequate treatment plans with good target volume coverage. However, the gain in target conformality should be balanced with the spread of low-doses to distant areas. This remains an open issue for the potential risk of secondary malignancies (SMNs) and longer follow-up is mandatory. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Figures

Open AccessArticle Peptide Based Vaccine Approaches for Cancer—A Novel Approach Using a WT-1 Synthetic Long Peptide and the IRX-2 Immunomodulatory Regimen
Cancers 2011, 3(4), 3991-4009; doi:10.3390/cancers3043991
Received: 15 August 2011 / Revised: 13 October 2011 / Accepted: 14 October 2011 / Published: 25 October 2011
Cited by 5 | PDF Full-text (212 KB) | HTML Full-text | XML Full-text
Abstract
Therapeutic cancer vaccines have the potential to generate a long lasting immune response that will destroy tumor cells with specificity and safety, in contrast to many other current cancer therapies. Clinical success to date has been limited by a number of factors [...] Read more.
Therapeutic cancer vaccines have the potential to generate a long lasting immune response that will destroy tumor cells with specificity and safety, in contrast to many other current cancer therapies. Clinical success to date has been limited by a number of factors including choice of immunogenic cancer rejection antigens, optimization of vaccine platforms and immune adjuvants to effectively polarize the immune response, and incorporation of strategies to reverse cancer mediated immune suppression by utilization of effective adjuvant/immune modulators. WT-1 (Wilms’ tumor gene 1) is a cancer antigen that is required for tumorigenesis, expressed in a high percentage of tumor cells and rarely expressed in adult normal cells. Moreover spontaneous immunity to WT-1 is seen in cancer patients and can be augmented with various therapeutic vaccine approaches. IRX-2 is an immune modulator with demonstrated preclinical and clinical pleiotropic immune activities including enhancement of the immune response to potential tumor antigens. This paper presents the rationale and preclinical data for utilizing the WT-1 tumor antigen in a novel vaccine platform consisting of a synthetic long peptide containing multiple class I and class II epitopes in combination with the IRX-2 immunomodulatory regimen to overcome immuno-suppressive pathways and enhance the anti-tumor response. Full article
(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy)
Open AccessArticle Carbon Ion Radiotherapy at the Gunma University Heavy Ion Medical Center: New Facility Set-up
Cancers 2011, 3(4), 4046-4060; doi:10.3390/cancers3044046
Received: 18 August 2011 / Revised: 30 September 2011 / Accepted: 13 October 2011 / Published: 26 October 2011
Cited by 23 | PDF Full-text (632 KB) | HTML Full-text | XML Full-text
Abstract
Carbon ion radiotherapy (C-ion RT) offers superior dose conformity in the treatment of deep-seated tumors compared with conventional X-ray therapy. In addition, carbon ion beams have a higher relative biological effectiveness compared with protons or X-ray beams. C-ion RT for the first [...] Read more.
Carbon ion radiotherapy (C-ion RT) offers superior dose conformity in the treatment of deep-seated tumors compared with conventional X-ray therapy. In addition, carbon ion beams have a higher relative biological effectiveness compared with protons or X-ray beams. C-ion RT for the first patient at Gunma University Heavy Ion Medical Center (GHMC) was initiated in March of 2010. The major specifications of the facility were determined based on the experience of clinical treatments at the National Institute of Radiological Sciences (NIRS), with the size and cost being reduced to one-third of those at NIRS. The currently indicated sites of cancer treatment at GHMC are lung, prostate, head and neck, liver, rectum, bone and soft tissue. Between March 2010 and July 2011, a total of 177 patients were treated at GHMC although a total of 100 patients was the design specification during the period in considering the optimal machine performance. In the present article, we introduce the facility set-up of GHMC, including the facility design, treatment planning systems, and clinical preparations. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessArticle Discriminating Different Cancer Cells Using a Zebrafish in Vivo Assay
Cancers 2011, 3(4), 4102-4113; doi:10.3390/cancers3044102
Received: 8 September 2011 / Revised: 13 October 2011 / Accepted: 21 October 2011 / Published: 31 October 2011
Cited by 7 | PDF Full-text (1472 KB) | HTML Full-text | XML Full-text
Abstract
Despite the expanded understanding of tumor angiogenesis phenomenon and how it impacts cancer treatment outcomes, we have yet to develop a robust assay that can quickly, easily, and quantitatively measure tumor-induced angiogenesis. Since the zebrafish/tumor xenograft represents an emerging tool in this [...] Read more.
Despite the expanded understanding of tumor angiogenesis phenomenon and how it impacts cancer treatment outcomes, we have yet to develop a robust assay that can quickly, easily, and quantitatively measure tumor-induced angiogenesis. Since the zebrafish/tumor xenograft represents an emerging tool in this regard, the present study strives to capitalize on the ease, effectiveness, and the adaptability of this model to quantify tumor angiogenesis. In order to test a range of responses, we chose two different tumorigenic cell lines, the human non-small cell lung carcinoma (H1299) and the mouse lung adenocarcinoma (CL13). Non-tumorigenic 3T3-L1 cells served as negative control. The cells were grafted near to the perivitelline space of the zebrafish embryos and the angiogenic response was analyzed using whole-mount alkaline phosphatase (AP) vessel staining and fluorescence microscopy. Angiogenic activity was scored based on the length and number of the newly formed ectopic vessels and the percentage of embryos with ectopic vessels. At 2 day-post-implantation, we detected a significant increase in the length and number of ectopic vessels with H1299 cell implantation compared to CL13 cell transplantation, both are higher than 3T3-L1 control. We also observed a significantly higher percentage of embryos with ectopic vessels with H1299 and CL13 transplantation compared to the 3T3-L1 control, but this parameter is not as robust and reliable as measuring the length and number of ectopic vessels. Furthermore, the systemic exposure of zebrafish embryos to an anti-angiogenesis drug (PTK 787, inhibitor of vascular endothelial growth factor receptor tyrosine kinase) inhibited tumor-induced angiogenesis, suggesting that the assay can be used to evaluate anti-angiogenic drugs. This study implicates the feasibility of using zebrafish xenotransplantation to perform quantitative measurement of the angiogenic activity of cancer cells which can be further extended to measure cancer cell metastasis. This assay represents not only the useful test for patient diagnosis, but also has the potential for evaluating anti-cancer drugs treatment. Full article
(This article belongs to the Special Issue Tumor Stroma)
Open AccessArticle Distribution of Functional Liver Volume in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus in the 1st Branch and Main Trunk Using Single Photon Emission Computed Tomography—Application to Radiation Therapy
Cancers 2011, 3(4), 4114-4126; doi:10.3390/cancers3044114
Received: 22 September 2011 / Revised: 22 October 2011 / Accepted: 22 October 2011 / Published: 31 October 2011
PDF Full-text (803 KB) | HTML Full-text | XML Full-text
Abstract
Purpose: To analyze the distribution of functional liver volume (FLV) in the margin volume (MV) surrounding hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) before radiation therapy (RT) and to verify the safety of single photon emission computed tomography-based three-dimensional conformal radiotherapy (SPECT-B3DCRT) by exploring the relation of FLV in MV to radiation-induced liver disease (RILD). Methods and Materials: Clinical target volume (CTV) included main tumor and PVTT, and planning target volume (PTV) included CTV with a 10 mm margin. MV was defined as PTV–CTV. FLV ratio in MV was calculated as FLV in MV/MV × 100 (%). The two high-dose beams were planned to irradiate FLV as little as possible. Fifty-seven cases of HCC (26/57, 46%; Child–Pugh grade B) with PVTT underwent SPECT-B3DCRT which targeted the CTV to a total dose of 45 Gy/18 fractions. The destructive ratio was defined as radiation induced dysfunctional volume/FLV × 100 (%). Results: We observed a significant negative correlation between FLV ratio in MV and CTV (p < 0.001). Three cases with CTVs of 287, 587 and 1184 cm3 experienced transient RILD. The FLV ratio in MV was highest in patients with RILD: nine patients with CTV of 200–300 cm3, three with CTV of 500–600 cm3, and two with CTV of 1100–1200 cm3. The destructive ratio yielded a mean value of 24.2 ± 1.5%. Conclusions: Radiation planning that takes into account the distribution of FLV appears to result in the least possible RILD. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessArticle Risk of Prostate Cancer after Trans Urethral Resection of BPH: A Cohort and Nested Case-Control Study
Cancers 2011, 3(4), 4127-4138; doi:10.3390/cancers3044127
Received: 14 September 2011 / Revised: 24 October 2011 / Accepted: 28 October 2011 / Published: 8 November 2011
Cited by 1 | PDF Full-text (623 KB) | HTML Full-text | XML Full-text
Abstract
Epidemiological and experimental evidence suggests that inflammation plays a role in both prostate cancer (PCa) and benign prostate hyperplasia (BPH). This study evaluates the risk of PC after transurethral resection (TURP) for BPH and estimates the PCa risk related to presence of [...] Read more.
Epidemiological and experimental evidence suggests that inflammation plays a role in both prostate cancer (PCa) and benign prostate hyperplasia (BPH). This study evaluates the risk of PC after transurethral resection (TURP) for BPH and estimates the PCa risk related to presence of inflammation in the resected material. The Pathology Department at the University Hospital of Umeå (Umeå, Sweden) identified BPH cases (n = 7,901) that underwent TURP between 1982 and 1997. Using these pathological specimens, we compared the incidence of PCa in the cohort to the population and calculated the standardized incidence and mortality ratios (SIR and SMR). Inflammation, the androgen receptor (AR), and p53 were evaluated in a nested case-control study of 201 cases and controls. Inflammation was graded severe or mild-moderate. In the follow-up period after TURP, cases developed prostate cancer and the controls did not. After TURP, SIR for prostate cancer increased [1.26, CI 95% (1.17–1.35)], whereas SMR decreased [0.59, CI 95% (0.47–0.73)]. Presence of inflammation at the time of TURP did not differ between cases and controls nor were there differences in p53 or AR staining. The data suggest a small increased risk of PCa after TURP and decreased PCa mortality. Inflammation at the time of TURP is not associated with PCa risk in this material. The increased PCa risk may be attributed to increased surveillance and PSA screening. Full article
(This article belongs to the Special Issue Prostate Cancer)
Open AccessArticle Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology
Cancers 2011, 3(4), 4151-4169; doi:10.3390/cancers3044151
Received: 17 October 2011 / Revised: 3 November 2011 / Accepted: 7 November 2011 / Published: 11 November 2011
Cited by 6 | PDF Full-text (723 KB) | HTML Full-text | XML Full-text
Abstract
Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of [...] Read more.
Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses. Full article
(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy)
Open AccessArticle Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer
Cancers 2011, 3(4), 4212-4227; doi:10.3390/cancers3044212
Received: 2 October 2011 / Revised: 24 November 2011 / Accepted: 30 November 2011 / Published: 6 December 2011
Cited by 4 | PDF Full-text (934 KB) | HTML Full-text | XML Full-text
Abstract
Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA [...] Read more.
Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa)—the 70 gene signature MammaPrint® and the five gene Molecular Grade Index (MGISM). Our aim was to assess the immunohistochemical (IHC) expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM) estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS). Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02) in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei) was 79% compared to 85% in low expression tumors ( 60.07; p = 0.06) within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker. Full article
Open AccessArticle A Novel Therapeutic Strategy for the Treatment of Glioma, Combining Chemical and Molecular Targeting of Hsp90a
Cancers 2011, 3(4), 4228-4244; doi:10.3390/cancers3044228
Received: 21 October 2011 / Revised: 21 November 2011 / Accepted: 30 November 2011 / Published: 8 December 2011
Cited by 4 | PDF Full-text (442 KB) | HTML Full-text | XML Full-text
Abstract
Hsp90a’s vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90a was downregulated using the post-transcriptional RNAi strategy (sihsp90a) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90a, 17-AAG and concurrent sihsp90a/17-AAG (combined treatment). Both Hsp90a gene silencing and the protein inhibitor approaches resulted in a dramatic reduction in cell viability. Results showed that sihsp90a, 17-AAG and a combination of sihsp90a/17-AAG, reduced cell viability by 27%, 75% and 88% (p < 0.001), respectively, after 72 h. hsp90a mRNA copy numbers were downregulated by 65%, 90% and 99% after 72 h treatment with sihsp90a, 17-AAG and sihsp90a/17-AAG, respectively. The relationship between Hsp90a protein expression and its client Akt kinase activity levels were monitored following treatment with sihsp90a, 17-AAG and sihsp90a/17-AAG. Akt kinase activity was downregulated as a direct consequence of Hsp90a inhibition. Both Hsp90a and Akt kinase levels were significantly downregulated after 72 h. Although, 17-AAG when used as a single agent reduces the Hsp90a protein and the Akt kinase levels, the efficacy demonstrated by combinatorial treatment was found to be far more effective. Combination treatment reduced the Hsp90a protein and Akt kinase levels to 4.3% and 43%, respectively, after 72 h. hsp90a mRNA expression detected in SVGp12 was negligible compared to U87-MG, also, the combination treatment did not compromise the normal cell viability. Taking into account the role of Hsp90a in tumour progression and the involvement of Akt kinase in cell signalling and the anti-apoptotic pathways in tumours, this double targets treatment infers a novel therapeutic strategy. Full article
Open AccessArticle Clinical Investigation of the Role of Interleukin-4 and Interleukin-13 in the Evolution of Prostate Cancer
Cancers 2011, 3(4), 4281-4293; doi:10.3390/cancers3044281
Received: 24 October 2011 / Revised: 23 November 2011 / Accepted: 30 November 2011 / Published: 16 December 2011
Cited by 3 | PDF Full-text (491 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer is the most common cancer in men, both in the USA and Europe. Although incurable, metastatic disease can often be controlled for years with anti-androgen therapy. Once the disease becomes castrate resistant, the median survival is 18 months. There is [...] Read more.
Prostate cancer is the most common cancer in men, both in the USA and Europe. Although incurable, metastatic disease can often be controlled for years with anti-androgen therapy. Once the disease becomes castrate resistant, the median survival is 18 months. There is growing evidence that the immune system, and in particular cytokines, play an important role in prostate cancer immunosurveillance and progression. Here, we have undertaken a clinical investigation of the role of two closely related cytokines, IL-4 and IL-13 in prostate cancer. In the largest series studied to date, we show that serum IL-4, but not IL-13 is significantly elevated in castrate resistant, compared to androgen sensitive disease. Notably however, serum IL-4 levels are also raised in patients with benign prostatic disease. Analysis of benign and malignant prostate tissue demonstrates that the source of IL-4 is epithelial cells rather than infiltrating leukocytes. Together, our data are consistent with a dual role for IL-4 in prostate cancer development. In benign disease, our data add to the evidence that IL-4 serves a protective role. By contrast, the data support a direct role for IL-4 in the progression of prostate cancer from androgen responsive, to advanced castrate-resistant disease. Full article
(This article belongs to the Special Issue Immune Responses to Human Prostate Cancer)

Review

Jump to: Research

Open AccessReview Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma
Cancers 2011, 3(4), 3740-3761; doi:10.3390/cancers3043740
Received: 31 August 2011 / Revised: 15 September 2011 / Accepted: 19 September 2011 / Published: 28 September 2011
Cited by 12 | PDF Full-text (1493 KB) | HTML Full-text | XML Full-text
Abstract
Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature [...] Read more.
Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression. Full article
(This article belongs to the Special Issue Exploring Inflammation in Cancers)
Open AccessReview Biomarkers in Prostate Cancer Epidemiology
Cancers 2011, 3(4), 3773-3798; doi:10.3390/cancers3043773
Received: 1 August 2011 / Revised: 26 September 2011 / Accepted: 26 September 2011 / Published: 30 September 2011
Cited by 12 | PDF Full-text (281 KB) | HTML Full-text | XML Full-text
Abstract
Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual [...] Read more.
Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed. Full article
(This article belongs to the Special Issue Prostate Cancer)
Open AccessReview Combined Hyperthermia and Radiotherapy for the Treatment of Cancer
Cancers 2011, 3(4), 3799-3823; doi:10.3390/cancers3043799
Received: 15 July 2011 / Revised: 23 September 2011 / Accepted: 23 September 2011 / Published: 30 September 2011
Cited by 15 | PDF Full-text (182 KB) | HTML Full-text | XML Full-text
Abstract
Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an in­tegral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse [...] Read more.
Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an in­tegral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, car­diac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threat­ening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic alterations in tumors and the development of treatments combining pharmacological interventions with ionizing radiation that more specifically target either tumor or normal tissue, leading to improvements in efficacy. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessReview Targeted Radionuclide Therapy
Cancers 2011, 3(4), 3838-3855; doi:10.3390/cancers3043838
Received: 22 August 2011 / Revised: 27 September 2011 / Accepted: 27 September 2011 / Published: 11 October 2011
Cited by 15 | PDF Full-text (289 KB) | HTML Full-text | XML Full-text
Abstract
Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to [...] Read more.
Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose. Full article
(This article belongs to the Special Issue Cancer Diagnosis and Targeted Therapy)
Open AccessReview Cytokines in Cancer Immunotherapy
Cancers 2011, 3(4), 3856-3893; doi:10.3390/cancers3043856
Received: 16 August 2011 / Revised: 24 September 2011 / Accepted: 27 September 2011 / Published: 13 October 2011
Cited by 41 | PDF Full-text (369 KB) | HTML Full-text | XML Full-text
Abstract
Cytokines are molecular messengers that allow the cells of the immune system to communicate with one another to generate a coordinated, robust, but self-limited response to a target antigen. The growing interest over the past two decades in harnessing the immune system [...] Read more.
Cytokines are molecular messengers that allow the cells of the immune system to communicate with one another to generate a coordinated, robust, but self-limited response to a target antigen. The growing interest over the past two decades in harnessing the immune system to eradicate cancer has been accompanied by heightened efforts to characterize cytokines and exploit their vast signaling networks to develop cancer treatments. The goal of this paper is to review the major cytokines involved in cancer immunotherapy and discuss their basic biology and clinical applications. The paper will also describe new cytokines in pre-clinical development, combinations of biological agents, novel delivery mechanisms, and potential directions for future investigation using cytokines. Full article
(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy)
Open AccessReview The Crosstalk of PTGS2 and EGF Signaling Pathways in Colorectal Cancer
Cancers 2011, 3(4), 3894-3908; doi:10.3390/cancers3043894
Received: 13 September 2011 / Revised: 7 October 2011 / Accepted: 9 October 2011 / Published: 14 October 2011
Cited by 15 | PDF Full-text (231 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancer (CRC) is now the second-leading cause of cancer deaths in the USA. Colorectal cancer progression and metastasis depends on the orchestration of the aberrant signaling pathways that control tumor cell proliferation, survival and migration/invasion. Epidemiological, clinical, and animal studies have [...] Read more.
Colorectal cancer (CRC) is now the second-leading cause of cancer deaths in the USA. Colorectal cancer progression and metastasis depends on the orchestration of the aberrant signaling pathways that control tumor cell proliferation, survival and migration/invasion. Epidemiological, clinical, and animal studies have demonstrated that prostaglandin-endoperoxide synthase 2 (PTGS2) and epithelial growth factor (EGF) signaling pathways play key roles in promoting colorectal cancer growth and metastasis. In this review, we highlight major advances in our understanding of the roles of PTGS2 and EGF signaling in colorectal cancer. Full article
(This article belongs to the Special Issue Exploring Inflammation in Cancers)
Open AccessReview Inducible Hsp70 in the Regulation of Cancer Cell Survival: Analysis of Chaperone Induction, Expression and Activity
Cancers 2011, 3(4), 3921-3956; doi:10.3390/cancers3043921
Received: 30 June 2011 / Revised: 26 September 2011 / Accepted: 10 October 2011 / Published: 21 October 2011
Cited by 10 | PDF Full-text (885 KB) | HTML Full-text | XML Full-text
Abstract
Understanding the mechanisms that control stress is central to realize how cells respond to environmental and physiological insults. All the more important is to reveal how tumour cells withstand their harsher growth conditions and cope with drug-induced apoptosis, since resistance to chemotherapy [...] Read more.
Understanding the mechanisms that control stress is central to realize how cells respond to environmental and physiological insults. All the more important is to reveal how tumour cells withstand their harsher growth conditions and cope with drug-induced apoptosis, since resistance to chemotherapy is the foremost complication when curing cancer. Intensive research on tumour biology over the past number of years has provided significant insights into the molecular events that occur during oncogenesis, and resistance to anti-cancer drugs has been shown to often rely on stress response and expression of inducible heat shock proteins (HSPs). However, with respect to the mechanisms guarding cancer cells against proteotoxic stresses and the modulatory effects that allow their survival, much remains to be defined. Heat shock proteins are molecules responsible for folding newly synthesized polypeptides under physiological conditions and misfolded proteins under stress, but their role in maintaining the transformed phenotype often goes beyond their conventional chaperone activity. Expression of inducible HSPs is known to correlate with limited sensitivity to apoptosis induced by diverse cytotoxic agents and dismal prognosis of several tumour types, however whether cancer cells survive because of the constitutive expression of heat shock proteins or the ability to induce them when adapting to the hostile microenvironment remains to be elucidated. Clear is that tumours appear nowadays more “addicted” to heat shock proteins than previously envisaged, and targeting HSPs represents a powerful approach and a future challenge for sensitizing tumours to therapy. This review will focus on the anti-apoptotic role of heat shock 70kDa protein (Hsp70), and how regulatory factors that control inducible Hsp70 synthesis, expression and activity may be relevant for response to stress and survival of cancer cells. Full article
(This article belongs to the Special Issue Cell Death and Cancer)
Open AccessReview Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells
Cancers 2011, 3(4), 3957-3971; doi:10.3390/cancers3043957
Received: 25 August 2011 / Revised: 1 October 2011 / Accepted: 13 October 2011 / Published: 24 October 2011
Cited by 3 | PDF Full-text (168 KB) | HTML Full-text | XML Full-text
Abstract
Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure [...] Read more.
Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a critical role in embryonic and inducible pluripotent stem cell regulation and emerging evidence supports their role in cancer stem cell evolution. To date, miRNAs have been shown to act either as tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including hematopoietic and epithelial tumors and sarcomas. miRNAs involved in cancer stem cell regulation provide attractive, novel therapeutic targets for cancer treatment. This review attempts to summarize progress to date in defining the role of miRNAs in cancer stem cells. Full article
Open AccessReview Role of Radiation Therapy in the Management of Renal Cell Cancer
Cancers 2011, 3(4), 4010-4023; doi:10.3390/cancers3044010
Received: 8 August 2011 / Revised: 11 October 2011 / Accepted: 19 October 2011 / Published: 26 October 2011
Cited by 11 | PDF Full-text (100 KB) | HTML Full-text | XML Full-text
Abstract
Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic [...] Read more.
Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS) for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT) with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR) inhibitors, to maximize both local and systemic control. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessReview Nanoparticle Delivery of Natural Products in the Prevention and Treatment of Cancers: Current Status and Future Prospects
Cancers 2011, 3(4), 4024-4045; doi:10.3390/cancers3044024
Received: 21 July 2011 / Revised: 15 September 2011 / Accepted: 17 October 2011 / Published: 26 October 2011
Cited by 10 | PDF Full-text (150 KB) | HTML Full-text | XML Full-text
Abstract
The advent of nanotechnology has had a revolutionary impact on many aspects of 21st century life. Nanotechnology has provided an opportunity to explore new avenues that conventional technologies have been unable to make an impact on for diagnosis, prevention, and therapy [...] Read more.
The advent of nanotechnology has had a revolutionary impact on many aspects of 21st century life. Nanotechnology has provided an opportunity to explore new avenues that conventional technologies have been unable to make an impact on for diagnosis, prevention, and therapy of different diseases, and of cancer in particular. Entities in nanometer sizes are excellent platforms to incorporate various drugs or active materials that can be delivered effectively to the desired action site without compromising the activity of the incorporated drug or material. In particular, nanotechnology entities can be used to deliver conventional natural products that have poor solubility or a short half life. Conventional natural products used with entities in nanometer sizes enable us to solve many of the inherent problems (stability, solubility, toxicity) associated with natural products, and also provide a platform for targeted delivery to tumor sites. We recently introduced the novel concept of using nanotechnology for enhancing the outcome of chemoprevention, which we called ‘nanochemoprevention’. This idea was subsequently exploited by several laboratories worldwide and has now become an advancing field in chemoprevention research. This review examines some of the applications of nanotechnology for cancer prevention and therapy using natural products. Full article
Open AccessReview A Review of the Role of Re-Irradiation in Recurrent High-Grade Glioma (HGG)
Cancers 2011, 3(4), 4061-4089; doi:10.3390/cancers3044061
Received: 5 August 2011 / Revised: 8 October 2011 / Accepted: 21 October 2011 / Published: 28 October 2011
Cited by 3 | PDF Full-text (244 KB) | HTML Full-text | XML Full-text
Abstract
Despite the use of more effective multimodal treatments in high-grade glioma (HGG), the outcome of patients affected by this disease is still dismal and recurrence is a very common event. Many therapeutic approaches, alone or combined (surgery, drugs, targeted agents, immunotherapy, radiotherapy, [...] Read more.
Despite the use of more effective multimodal treatments in high-grade glioma (HGG), the outcome of patients affected by this disease is still dismal and recurrence is a very common event. Many therapeutic approaches, alone or combined (surgery, drugs, targeted agents, immunotherapy, radiotherapy, supportive therapy), are available in the clinical armamentarium so far. The attitude of physicians is increasingly interventionist, but recurrent HGG still remains a very difficult scenario to be treated. Radiotherapy with different re-irradiation techniques is increasingly proposed as a therapeutic option with interesting results, even though the resulting duration of response is usually quite short. Most lesions re-recur locally, with inadequate identification and targeting of viable tumor being the most important cause of failure. Prognosis is affected by many patient-, tumor-, and treatment-associated prognostic factors. Radiotherapy is delivered with many advanced modalities: 3D-CRT, intensity-modulated radiation therapy, stereotactic fractionated radiotherapy, radiosurgery, and brachitherapy with or without chemotherapy administration. In order to evaluate the feasibility and efficacy of re-irradiation in this setting, we reviewed the PubMed and MEDLINE databases restricting the search to original reports published from January 1990 to June 2011. The search resulted in a total of 155 reports: 78 of them covering 2,688 patients treated with different irradiation modalities overall fulfilled the entry criteria. Radiation therapy demonstrated to be an acceptable option in recurrent HGG with good response rates and acceptable toxicity. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessReview The Utility of Proton Beam Therapy with Concurrent Chemotherapy for the Treatment of Esophageal Cancers
Cancers 2011, 3(4), 4090-4101; doi:10.3390/cancers3044090
Received: 7 September 2011 / Revised: 17 October 2011 / Accepted: 20 October 2011 / Published: 28 October 2011
PDF Full-text (1366 KB) | HTML Full-text | XML Full-text
Abstract
The standard of care for the management of locally advanced esophageal cancers in the United States is chemotherapy combined with radiation, either definitively, or for those who could tolerate surgery, preoperatively before esophagectomy. Although the appropriate radiation dose remains somewhat controversial, the [...] Read more.
The standard of care for the management of locally advanced esophageal cancers in the United States is chemotherapy combined with radiation, either definitively, or for those who could tolerate surgery, preoperatively before esophagectomy. Although the appropriate radiation dose remains somewhat controversial, the quality of the radiation delivery is critical for the treatment of esophageal cancer since the esophagus is positioned close to vital structures, such as the heart and lung. The volume and relative doses to these normal tissues affect acute and late term complications. Advances in radiation delivery from 2D to 3D conformal radiation therapy, to Intensity Modulated Radiation Therapy (IMRT) or charged particle therapy (carbon ion or proton beam therapy (PBT)), allow incremental improvements in the therapeutic ratio. This could have implications in non-cancer related morbidity for long term survivors. This article reviews the evolution in radiation technologies and the use of PBT with chemotherapy in the management of esophageal cancer. Full article
(This article belongs to the Special Issue Radiation and Cancers)
Open AccessReview Sarcoma Immunotherapy
Cancers 2011, 3(4), 4139-4150; doi:10.3390/cancers3044139
Received: 6 September 2011 / Revised: 19 October 2011 / Accepted: 19 October 2011 / Published: 10 November 2011
PDF Full-text (184 KB) | HTML Full-text | XML Full-text
Abstract
Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The [...] Read more.
Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis. Full article
(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy)
Open AccessReview Transcription Inhibition as a Therapeutic Target for Cancer
Cancers 2011, 3(4), 4170-4190; doi:10.3390/cancers3044170
Received: 18 July 2011 / Revised: 14 November 2011 / Accepted: 16 November 2011 / Published: 23 November 2011
Cited by 14 | PDF Full-text (542 KB) | HTML Full-text | XML Full-text
Abstract
During tumorigenesis the transformed cells lose their normal growth control mechanisms and become dependent on oncogenes’ products and pathways for survival. Treatments tailored to block the expression or function of transforming genes have shown efficacy in eliminating neoplastic cells. The mRNAs of [...] Read more.
During tumorigenesis the transformed cells lose their normal growth control mechanisms and become dependent on oncogenes’ products and pathways for survival. Treatments tailored to block the expression or function of transforming genes have shown efficacy in eliminating neoplastic cells. The mRNAs of many oncogenes, as well as regulators of other key processes such as cell proliferation, angiogenesis, and apoptosis, typically have shorter half-lives. Agents that impede mRNA synthesis are expected to selectively hinder the expression of these genes and, therefore, be detrimental to neoplastic cells that are physiologically dependent on them. In addition to exploiting the tumor cells’ dependency on short-lived transcripts, RNA-directed agents also take advantage of the differential sensitivity between transformed and non-transformed cells, as the cytotoxic effects of inhibiting RNA synthesis have not been seen in non-transformed cells. The abrogation of the formation of oncotranscripts provides a new concept in cancer therapeutics and numerous agents have been developed which are able to target transcription. The focus of this review is to give an overview of transcription and the different inhibitory strategies that target various aspects of the transcriptional process. Full article
(This article belongs to the Special Issue Cancer Diagnosis and Targeted Therapy)
Open AccessReview Cancer Genome Sequencing and Its Implications for Personalized Cancer Vaccines
Cancers 2011, 3(4), 4191-4211; doi:10.3390/cancers3044191
Received: 17 September 2011 / Revised: 31 October 2011 / Accepted: 9 November 2011 / Published: 25 November 2011
Cited by 2 | PDF Full-text (1337 KB) | HTML Full-text | XML Full-text
Abstract
New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making [...] Read more.
New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making with the potential to affect diagnosis, prognosis, and treatment, and has opened the door towards personalized medicine. A promising strategy is the identification of mutated tumor antigens, and the design of personalized cancer vaccines. Supporting this notion are preliminary analyses of the epitope landscape in breast cancer suggesting that individual tumors express significant numbers of novel antigens to the immune system that can be specifically targeted through cancer vaccines. Full article
(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy)
Figures

Open AccessReview Stroma-Directed Molecular Targeted Therapy in Gastric Cancer
Cancers 2011, 3(4), 4245-4257; doi:10.3390/cancers3044245
Received: 11 October 2011 / Revised: 22 November 2011 / Accepted: 30 November 2011 / Published: 8 December 2011
PDF Full-text (856 KB) | HTML Full-text | XML Full-text
Abstract
Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone, but also by a variety of stromal cells. Tumor stroma contains abundant extracellular matrix and several types of cells, including carcinoma-associated [...] Read more.
Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone, but also by a variety of stromal cells. Tumor stroma contains abundant extracellular matrix and several types of cells, including carcinoma-associated fibroblasts (CAFs), endothelial cells, pericytes and inflammatory cells including macrophages. In gastric cancer tissues, tumor cells express platelet-derived growth factor (PDGF)-B. Stromal cells, including CAFs, pericytes and lymphatic endothelial cells, express PDGF receptor (PDGFR)-β. Administration of PDGFR tyrosine kinase inhibitor significantly decreases stromal reaction, lymphatic vessel area and pericyte coverage of tumor microvessels. Administration of PDGFR tyrosine kinase inhibitor in combination with cytotoxic chemotherapeutic drug(s) impairs the progressive growth and metastasis of gastric cancer. Activated stroma might serve as a novel therapeutic target in cases of gastric cancer. Full article
(This article belongs to the Special Issue Tumor Stroma)
Open AccessReview NF-kappaB in Lung Tumorigenesis
Cancers 2011, 3(4), 4258-4268; doi:10.3390/cancers3044258
Received: 13 October 2011 / Revised: 29 November 2011 / Accepted: 6 December 2011 / Published: 14 December 2011
Cited by 4 | PDF Full-text (101 KB) | HTML Full-text | XML Full-text
Abstract
The development of lung cancer in humans can be divided into three steps: initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the [...] Read more.
The development of lung cancer in humans can be divided into three steps: initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis. Full article
(This article belongs to the Special Issue Lung Cancer)
Open AccessReview Actin—Towards a Deeper Understanding of the Relationship Between Tissue Context, Cellular Function and Tumorigenesis
Cancers 2011, 3(4), 4269-4280; doi:10.3390/cancers3044269
Received: 17 October 2011 / Revised: 26 November 2011 / Accepted: 7 December 2011 / Published: 14 December 2011
PDF Full-text (106 KB) | HTML Full-text | XML Full-text
Abstract
It is well-established that the actin cytoskeleton plays an important role in tumor development yet the contribution made by nuclear actin is ill-defined. In a recent study, nuclear actin was identified as a key mediator through which laminin type III (LN1) acts [...] Read more.
It is well-established that the actin cytoskeleton plays an important role in tumor development yet the contribution made by nuclear actin is ill-defined. In a recent study, nuclear actin was identified as a key mediator through which laminin type III (LN1) acts to control epithelial cell growth. In the breast, epithelial tumors are surrounded by an environment which lacks LN1. These findings point to actin as a potential mediator of tumor development. Here our current understanding of the roles of cytoplasmic and nuclear actin in normal and tumor cell growth is reviewed, relating these functions to cell phenotype in a tissue context. Full article
(This article belongs to the Special Issue Tumor Cell Genesis and Its Microenvironment: Chicken or the Egg)

Journal Contact

MDPI AG
Cancers Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
cancers@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Cancers
Back to Top