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Cancers, Volume 2, Issue 4 (December 2010), Pages 1771-2170

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Research

Jump to: Review, Other

Open AccessArticle Breast Cancer: Surgery at the South Egypt Cancer Institute
Cancers 2010, 2(4), 1771-1778; doi:10.3390/cancers2041771
Received: 3 August 2010 / Revised: 7 September 2010 / Accepted: 28 September 2010 / Published: 30 September 2010
Cited by 10 | PDF Full-text (222 KB) | HTML Full-text | XML Full-text
Abstract
Breast cancer is the most frequent malignant tumor in women worldwide. In Egypt, it is the most common cancer among women, representing 18.9% of total cancer cases (35.1% in women and 2.2% in men) among the Egypt National Cancer Institute’s (NCI) series [...] Read more.
Breast cancer is the most frequent malignant tumor in women worldwide. In Egypt, it is the most common cancer among women, representing 18.9% of total cancer cases (35.1% in women and 2.2% in men) among the Egypt National Cancer Institute’s (NCI) series of 10,556 patients during the year 2001, with an age-adjusted rate of 49.6 per 100,000 people. In this study, the data of all breast cancer patients presented to the surgical department of the South Egypt cancer Institute (SECI) hospital during the period from Janurary 2001 to December 2008 were reviewed .We report the progress of the availability of breast cancer management and evaluation of the quality of care delivered to breast cancer patients. The total number of patients with a breast lump presented to the SECI during the study period was 1,463 patients (32 males and 1431 females); 616 patients from the total number were admitted at the surgical department .There was a decline in advanced cases. Since 2001, facilities for all lines of comprehensive management have been made accessible for all patients. We found that better management could lead to earlier presentation, and better overall outcome in breast cancer patients.The incidence is steadily increasing with a tendency for breast cancer to occur in younger age groups and with advanced stages. Full article
Open AccessArticle CDDO-Me: A Novel Synthetic Triterpenoid for the Treatment of Pancreatic Cancer
Cancers 2010, 2(4), 1779-1793; doi:10.3390/cancers2041779
Received: 10 September 2010 / Revised: 8 October 2010 / Accepted: 11 October 2010 / Published: 13 October 2010
Cited by 10 | PDF Full-text (2299 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancy with dismal prognosis and few effective therapeutic options. Novel agents that are safe and effective are urgently needed. Oleanolic acid-derived synthetic triterpenoids are potent antitumorigenic agents, but their efficacy or [...] Read more.
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancy with dismal prognosis and few effective therapeutic options. Novel agents that are safe and effective are urgently needed. Oleanolic acid-derived synthetic triterpenoids are potent antitumorigenic agents, but their efficacy or the mechanism of action for pancreatic cancer has not been adequately investigated. In this study, we evaluated the antitumor activity and the mechanism of action of methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me), a oleanane-derived synthetic triterpenoid for human pancreatic cancer cell lines. CDDO-Me inhibited the growth of both K-ras mutated (MiaPaca2, Panc1 and Capan2) and wild-type K-ras (BxPC3) pancreatic cancer cells at very low concentrations. The growth inhibitory activity of CDDO-Me was attributed to the induction of apoptosis characterized by increased annexin-V-FITC binding and cleavage of PARP-1 and procaspases-3, -8 and-9. In addition, CDDO-Me induced the loss of mitochondrial membrane potential and release of cytochrome C. The antitumor activity of CDDO-Me was associated with the inhibition of prosurvival p-Akt, NF-κB and mammalian target of rapamycin (mTOR) signaling proteins and the downstream targets of Akt and mTOR, such as p-Foxo3a (Akt) and p-S6K1, p-eIF-4E and p-4E-BP1 (mTOR). Silencing of Akt or mTOR with gene specific-siRNA sensitized the pancreatic cancer cells to CDDO-Me, demonstrating Akt and mTOR as molecular targets of CDDO-Me for its growth inhibitory and apoptosis-inducing activity. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
Open AccessArticle Lung Cancer Susceptibility and hOGG1 Ser326Cys Polymorphism: A Meta-Analysis
Cancers 2010, 2(4), 1813-1829; doi:10.3390/cancers2041813
Received: 15 September 2010 / Revised: 15 October 2010 / Accepted: 24 October 2010 / Published: 28 October 2010
Cited by 2 | PDF Full-text (238 KB) | HTML Full-text | XML Full-text
Abstract
Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are [...] Read more.
Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using "hOGG1", "lung cancer" and "polymorphism" as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) model. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg’s and Egger’s tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among aucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9–22.9) and 46.1% (95% CI = 40.2–52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09–1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase in risk can translate to a large number of excess lung cancer cases. As lung cancer is a multifactorial disease, further investigations of the gene-gene and gene-environment interactions on the hOGG1 polymorphism-associated lung cancer risk may help to better understand of the molecular pathogenesis of human lung cancer. Full article
(This article belongs to the Special Issue Lung Cancer)
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Open AccessArticle Definition of Microscopic Tumor Clearance (R0) in Pancreatic Cancer Resections
Cancers 2010, 2(4), 2001-2010; doi:10.3390/cancers2042001
Received: 30 October 2010 / Accepted: 17 November 2010 / Published: 25 November 2010
Cited by 13 | PDF Full-text (298 KB) | HTML Full-text | XML Full-text
Abstract
To date, curative resection is the only chance for cure for patients suffering from pancreatic ductal adenoacarcinoma (PDAC). Despite low reported rates of microscopic tumor infiltration (R1) in most studies, tumor recurrence is a common finding in patients with PDAC and contributes [...] Read more.
To date, curative resection is the only chance for cure for patients suffering from pancreatic ductal adenoacarcinoma (PDAC). Despite low reported rates of microscopic tumor infiltration (R1) in most studies, tumor recurrence is a common finding in patients with PDAC and contributes to extremely low long-term survival rates. Lack of international definition of resection margins and of standardized protocols for pathological examination lead to high variation in reported R1 rates. Here we review recent studies supporting the hypothesis that R1 rates are highly underestimated in certain studies and that a microscopic tumor clearance of at least 1 mm is required to confirm radicality and to serve as a reliable prognostic and predictive factor. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
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Open AccessArticle A Distinct Slow-Cycling Cancer Stem-like Subpopulation of Pancreatic Adenocarcinoma Cells is maintained in Vivo
Cancers 2010, 2(4), 2011-2025; doi:10.3390/cancers2042011
Received: 8 October 2010 / Revised: 16 November 2010 / Accepted: 24 November 2010 / Published: 29 November 2010
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Abstract Pancreatic adenocarcinoma has the worst prognosis of any major malignancy, with Full article
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Open AccessArticle Targeting of Both the c-Met and EGFR Pathways Results in Additive Inhibition of Lung Tumorigenesis in Transgenic Mice
Cancers 2010, 2(4), 2153-2170; doi:10.3390/cancers2042153
Received: 20 October 2010 / Revised: 25 November 2010 / Accepted: 21 December 2010 / Published: 22 December 2010
Cited by 21 | PDF Full-text (1363 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
EGFR and c-Met are both overexpressed in lung cancer and initiate similar downstream signaling, which may be redundant. To determine how frequently ligands that initiate signaling of both pathways are found in lung cancer, we analyzed serum for hepatocyte growth factor (HGF), [...] Read more.
EGFR and c-Met are both overexpressed in lung cancer and initiate similar downstream signaling, which may be redundant. To determine how frequently ligands that initiate signaling of both pathways are found in lung cancer, we analyzed serum for hepatocyte growth factor (HGF), transforming growth factor-alpha, and amphiregulin (AREG) in lung cancer cases and tobacco-exposed controls. HGF and AREG were both significantly elevated in cases compared to controls, suggesting that both HGF/c-Met and AREG/EGFR pathways are frequently active. When both HGF and AREG are present in vitro, downstream signaling to MAPK and Akt in non-small cell lung cancer (NSCLC) cells can only be completely inhibited by targeting both pathways. To test if dual blockade of the pathways could better suppress lung tumorigenesis in an animal model than single blockade, mice transgenic for airway expression of human HGF were treated with inhibitors of both pathways alone and in combination after exposure to a tobacco carcinogen. Mean tumor number in the group using both the HGF neutralizing antibody L2G7 and the EGFR inhibitor gefitinib was significantly lower than with single agents. A higher tumor K-ras mutation rate was observed with L2G7 alone compared to controls, suggesting that agents targeting HGF may be less effective against mutated K-ras lung tumors. This was not observed with combination treatment. A small molecule c-Met inhibitor decreased formation of both K-ras wild-type and mutant tumors and showed additive anti-tumor effects when combined with gefitinib. Dual targeting of c-Met/EGFR may have clinical benefit for lung cancer. Full article
(This article belongs to the Special Issue Lung Cancer)
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Review

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Open AccessReview Mucins and Pancreatic Cancer
Cancers 2010, 2(4), 1794-1812; doi:10.3390/cancers2041794
Received: 17 September 2010 / Revised: 14 October 2010 / Accepted: 18 October 2010 / Published: 25 October 2010
Cited by 20 | PDF Full-text (373 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic cancer is characterized by an often dramatic outcome (five year survival < 5%) related to a late diagnosis and a lack of efficient therapy. Therefore, clinicians desperately need new biomarkers and new therapeutic tools to develop new efficient therapies. Mucins belong to an ever increasing family of O-glycoproteins. Secreted mucins are the main component of mucus protecting the epithelia whereas membrane-bound mucins are thought to play important biological roles in cell-cell and cell-matrix interactions, in cell signaling and in modulating biological properties of cancer cells. In this review, we will focus on the altered expression pattern of mucins in pancreatic cancer, from the early neoplastic lesion Pancreatic Intraepithelial Neoplasia (PanIN) to invasive pancreatic carcinomas, and the molecular mechanisms (including genetic and epigenetic regulation) and signaling pathways known to control their expression. Moreover, we will discuss the recent advances about the biology of both secreted and membrane-bound mucins and their key roles in pancreatic carcinogenesis and resistance to therapy. Finally, we will discuss exciting opportunities that mucins offer as potential therapeutic targets in pancreatic cancer. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
Open AccessReview Pancreatic Cancer Biomarkers and Their Implication in Cancer Diagnosis and Epidemiology
Cancers 2010, 2(4), 1830-1837; doi:10.3390/cancers2041830
Received: 21 October 2010 / Accepted: 29 October 2010 / Published: 2 November 2010
Cited by 3 | PDF Full-text (147 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic cancer is the fourth most common cause of cancer-related mortality in the United States. Biomarkers are needed to detect this cancer early during the disease development and for screening populations to identify those who are at risk. In cancer, “biomarker” refers [...] Read more.
Pancreatic cancer is the fourth most common cause of cancer-related mortality in the United States. Biomarkers are needed to detect this cancer early during the disease development and for screening populations to identify those who are at risk. In cancer, “biomarker” refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker might be either a molecule secreted by a tumor or it can be a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. A number of potential biomarkers have been identified for pancreatic cancer. These markers can be assayed in non-invasively collected biofluids. These biomarkers need analytical and clinical validation so that they can be used for the purpose of screening and diagnosing pancreatic cancer and determining disease prognosis. In this article, the latest developments in pancreatic cancer biomarkers are discussed. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
Open AccessReview NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells
Cancers 2010, 2(4), 1838-1860; doi:10.3390/cancers2041838
Received: 15 October 2010 / Revised: 3 November 2010 / Accepted: 4 November 2010 / Published: 5 November 2010
Cited by 2 | PDF Full-text (530 KB) | HTML Full-text | XML Full-text
Abstract
Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) [...] Read more.
Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL. Full article
(This article belongs to the Special Issue Cancer Diagnosis and Targeted Therapy)
Open AccessReview Familial Pancreatic Cancer
Cancers 2010, 2(4), 1861-1883; doi:10.3390/cancers2041861
Received: 12 October 2010 / Revised: 3 November 2010 / Accepted: 4 November 2010 / Published: 10 November 2010
Cited by 2 | PDF Full-text (429 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential [...] Read more.
Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
Open AccessReview Nanoparticles in Sentinel Lymph Node Assessment in Breast Cancer
Cancers 2010, 2(4), 1884-1894; doi:10.3390/cancers2041884
Received: 28 October 2010 / Revised: 2 November 2010 / Accepted: 9 November 2010 / Published: 17 November 2010
Cited by 5 | PDF Full-text (228 KB) | HTML Full-text | XML Full-text
Abstract
The modern management of the axilla in breast cancer relies on surgery for accurate staging of disease and identifying those patients at risk who would benefit from adjuvant chemotherapy. The introduction of sentinel lymph node biopsy has revolutionized axillary surgery, but still [...] Read more.
The modern management of the axilla in breast cancer relies on surgery for accurate staging of disease and identifying those patients at risk who would benefit from adjuvant chemotherapy. The introduction of sentinel lymph node biopsy has revolutionized axillary surgery, but still involves a surgical procedure with associated morbidity in many patients with no axillary involvement. Nanotechnology encompasses a broad spectrum of scientific specialities, of which nanomedicine is one. The potential use of dual-purpose nanoprobes could enable imaging the axilla simultaneous identification and treatment of metastatic disease. Whilst most applications of nanomedicine are still largely in the laboratory phase, some potential applications are currently undergoing clinical evaluation for translation from the bench to the bedside. This is an exciting new area of research where scientific research may become a reality. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
Open AccessReview Radiofrequency Ablation: A Minimally Invasive Approach in Kidney Tumor Management
Cancers 2010, 2(4), 1895-1900; doi:10.3390/cancers2041895
Received: 3 November 2010 / Revised: 8 November 2010 / Accepted: 11 November 2010 / Published: 17 November 2010
Cited by 1 | PDF Full-text (145 KB) | HTML Full-text | XML Full-text
Abstract
The management and diagnosis of renal tumors have changed significantly over the last decade. Due to advances in imaging techniques, more than 50% of kidney tumors are discovered incidentally and many of them represent an early stage lesion. This has stimulated the [...] Read more.
The management and diagnosis of renal tumors have changed significantly over the last decade. Due to advances in imaging techniques, more than 50% of kidney tumors are discovered incidentally and many of them represent an early stage lesion. This has stimulated the development of nephron-sparing surgery and of the minimally invasive treatment options including ablative techniques, i.e., radiofrequency ablation (RFA) and cryoablation. The objective of the minimally invasive approach is to preserve the renal function and to lower the perioperative morbidity. RFA involves inducing the coagulative necrosis of tumor tissue. Being probably one of the least invasive procedures in kidney tumor management, RFA may be performed percutaneously under ultrasound (US), computed tomography (CT) or magnetic resonance (MR) guidance. Most of the studies show that the RFA procedure is efficient, safe and has a low complication rate. Due to the still limited data on the oncological outcome of RFA, the indication for this intervention remains limited to selected patients with small organ-confined renal tumors and contraindication to surgery or who have a solitary kidney. The aim of our study is to review the literature on RFA of kidney tumors. Full article
Open AccessReview Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors
Cancers 2010, 2(4), 1901-1910; doi:10.3390/cancers2041901
Received: 19 October 2010 / Revised: 8 November 2010 / Accepted: 16 November 2010 / Published: 18 November 2010
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Abstract
Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET) or by symptoms related [...] Read more.
Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET) or by symptoms related to tumor bulk effects (non-functional PNET). So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
Open AccessReview A Comparative Study of Two Folate-Conjugated Gold Nanoparticles for Cancer Nanotechnology Applications
Cancers 2010, 2(4), 1911-1928; doi:10.3390/cancers2041911
Received: 29 October 2010 / Revised: 10 November 2010 / Accepted: 11 November 2010 / Published: 18 November 2010
Cited by 37 | PDF Full-text (815 KB) | HTML Full-text | XML Full-text
Abstract
We report a comparative study of synthesis, characteristics and in vitro tests of two folate-conjugated gold nanoparticles (AuNP) differing in linkers and AuNP sizes for selective targeting of folate-receptor positive cancerous cells. The linkers chosen were 4-aminothiophenol (4Atp) and 6-mercapto-1-hexanol [...] Read more.
We report a comparative study of synthesis, characteristics and in vitro tests of two folate-conjugated gold nanoparticles (AuNP) differing in linkers and AuNP sizes for selective targeting of folate-receptor positive cancerous cells. The linkers chosen were 4-aminothiophenol (4Atp) and 6-mercapto-1-hexanol (MH) with nanoconjugate products named Folate-4Atp-AuNP and Folate-MH-AuNP. We report the folate-receptor tissue distribution and its endocytosis for targeted nanotechnology. Comparison of the two nanoconjugates’ syntheses and characterization is also reported, including materials and methods of synthesis, UV-visible absorption spectroscopic measurements, Fourier Transform Infra Red (FTIR) measurements, Transmission electron microscopy (TEM) images and size distributions, X-ray diffraction data, elemental analyses and chemical stability comparison. In addition to the analytical characterization of the nanoconjugates, the cell lethality was measured in HeLa (high level of folate receptor expression) and MCF-7 (low level of folate receptor expression) cells. The nanoconjugates themselves, as well as the intense pulsed light (IPL) were not harmful to cell viability. However, upon stimulation of the folate targeted nanoconjugates with the IPL, ~98% cell killing was found in HeLa cells and only ~9% in MCF-7 cells after four hours incubation with the nanoconjugate. This demonstrates that folate targeting is effective in selecting for specific cell populations. Considering the various comparisons made, we conclude that Folate-4Atp-AuNP is superior to Folate-MH-AuNP for cancer therapy. Full article
(This article belongs to the Special Issue Nanotechnology and Cancer Therapeutics)
Open AccessReview Surgery as a Double-Edged Sword: A Clinically Feasible Approach to Overcome the Metastasis-Promoting Effects of Surgery by Blunting Stress and Prostaglandin Responses
Cancers 2010, 2(4), 1929-1951; doi:10.3390/cancers2041929
Received: 13 October 2010 / Revised: 14 November 2010 / Accepted: 23 November 2010 / Published: 24 November 2010
Cited by 10 | PDF Full-text (182 KB) | HTML Full-text | XML Full-text
Abstract
Surgery remains an essential therapeutic approach for most solid malignancies, including breast cancer. However, surgery also constitutes a risk factor for promotion of pre-existing micrometastases and the initiation of new metastases through several mechanisms, including the release of prostaglandins and stress hormones [...] Read more.
Surgery remains an essential therapeutic approach for most solid malignancies, including breast cancer. However, surgery also constitutes a risk factor for promotion of pre-existing micrometastases and the initiation of new metastases through several mechanisms, including the release of prostaglandins and stress hormones (e.g., catecholamines and glucocorticoids). However, the perioperative period also presents an opportunity for cell mediated immunity (CMI) and other mechanisms to eradicate or control minimal residual disease, provided that the deleterious effects of surgery are minimized. Here, we discuss the key role of endogenous stress hormones and prostaglandins in promoting the metastatic process through their direct impact on malignant cells, and through their deleterious impact on anti-cancer CMI. We further discuss the effects of anesthetic techniques, the extent of surgery, pain alleviation, and timing within the menstrual cycle with respect to their impact on tumor recurrence and physiological stress responses. Last, we suggest an attractive perioperative drug regimen, based on a combination of a cyclooxygenase (COX)-2 inhibitor and a β-adrenergic blocker, which we found effective in attenuating immune suppression and the metastasis-promoting effects of surgery in several tumor models. This regimen is clinically applicable, and could potentially promote disease free survival in patients operated for breast and other types of cancer. Full article
Open AccessReview The Enigmatic Roles of Caspases in Tumor Development
Cancers 2010, 2(4), 1952-1979; doi:10.3390/cancers2041952
Received: 8 November 2010 / Revised: 16 November 2010 / Accepted: 23 November 2010 / Published: 24 November 2010
Cited by 6 | PDF Full-text (195 KB) | HTML Full-text | XML Full-text
Abstract
One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the [...] Read more.
One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. From clinical data, however, there is little evidence that caspase genes are impaired in cancer. Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. These data seem to question a general tumor-suppressive role of caspases. We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream of caspase activation might be disrupted in tumor cells. Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. These scenarios, however, are hardly compatible with the considerable frequency of spontaneous apoptosis occurring in several cancer types. Therefore, alternative concepts might come into play, such as compensatory proliferation. Herein, apoptosis and/or non-apoptotic functions of caspases may even promote tumor development. Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors. Full article
(This article belongs to the Special Issue Cell Death and Cancer)
Open AccessReview Epidemiology of Skin Cancer: Role of Some Environmental Factors
Cancers 2010, 2(4), 1980-1989; doi:10.3390/cancers2041980
Received: 22 October 2010 / Revised: 11 November 2010 / Accepted: 17 November 2010 / Published: 24 November 2010
Cited by 3 | PDF Full-text (295 KB) | HTML Full-text | XML Full-text
Abstract
The incidence rate of melanoma and non-melanoma skin cancer entities is dramatically increasing worldwide. Exposure to UVB radiation is known to induce basal and squamous cell skin cancer in a dose-dependent way and the depletion of stratospheric ozone has implications for increases [...] Read more.
The incidence rate of melanoma and non-melanoma skin cancer entities is dramatically increasing worldwide. Exposure to UVB radiation is known to induce basal and squamous cell skin cancer in a dose-dependent way and the depletion of stratospheric ozone has implications for increases in biologically damaging solar UVB radiation reaching the earth’s surface. In humans, arsenic is known to cause cancer of the skin, as well as cancer of the lung, bladder, liver, and kidney. Exposure to high levels of arsenic in drinking water has been recognized in some regions of the world. SCC and BCC (squamous and basal cell carcinoma) have been reported to be associated with ingestion of arsenic alone or in combination with other risk factors. The impact of changes in ambient temperature will influence people’s behavior and the time they spend outdoors. Higher temperatures accompanying climate change may lead, among many other effects, to increasing incidence of skin cancer. Full article
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Open AccessReview Selection and Outcome of Portal Vein Resection in Pancreatic Cancer
Cancers 2010, 2(4), 1990-2000; doi:10.3390/cancers2041990
Received: 12 October 2010 / Revised: 11 November 2010 / Accepted: 22 November 2010 / Published: 24 November 2010
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Abstract
Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five-year survival of pancreatic cancer after pancreatectomy is very low, and surgical resection is the only option to cure this dismal disease. The standard surgical procedure is pancreatoduodenectomy (PD) for pancreatic head [...] Read more.
Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five-year survival of pancreatic cancer after pancreatectomy is very low, and surgical resection is the only option to cure this dismal disease. The standard surgical procedure is pancreatoduodenectomy (PD) for pancreatic head cancer. The morbidity and especially the mortality of PD have been greatly reduced. Portal vein resection in pancreatic cancer surgery is one attempt to increase resectability and radicality, and the procedure has become safe to perform. Clinicohistopathological studies have shown that the most important indication for portal vein resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, portal vein resection is contraindicated. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
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Open AccessReview Possible Role of Autophagy in the Treatment of Pancreatic Cancer with Histone Deacetylase Inhibitors
Cancers 2010, 2(4), 2026-2043; doi:10.3390/cancers2042026
Received: 18 October 2010 / Revised: 9 November 2010 / Accepted: 22 November 2010 / Published: 29 November 2010
Cited by 2 | PDF Full-text (135 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic cancer is a lethal disease and notoriously difficult to treat. Only a small proportion is curative by surgical resection, whilst standard chemotherapy for patients with advanced disease has only a modest effect with substantial toxicity. Clearly there is a need for [...] Read more.
Pancreatic cancer is a lethal disease and notoriously difficult to treat. Only a small proportion is curative by surgical resection, whilst standard chemotherapy for patients with advanced disease has only a modest effect with substantial toxicity. Clearly there is a need for the continual development of novel therapeutic agents to improve the current situation. Currently, there is a bulk of data indicating the important function of autophagy in cancer. While genetic evidence indicates that autophagy functions as a tumor suppressor, it is also apparent that autophagy can promote the survival of established tumors under stress conditions and in response to chemotherapy. This review provides a spectrum of potential pharmacological agents and autophagic approaches to enhance cell killing in pancreatic cancer. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
Open AccessReview Human Equilibrative Nucleoside Transporter 1 (hENT1) in Pancreatic Adenocarcinoma: Towards Individualized Treatment Decisions
Cancers 2010, 2(4), 2044-2054; doi:10.3390/cancers2042044
Received: 22 October 2010 / Revised: 29 November 2010 / Accepted: 30 November 2010 / Published: 2 December 2010
Cited by 6 | PDF Full-text (141 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic cancer is one of the most lethal cancers, where curative surgical resections are rare and less than 5% of patients experience long-term survival. Despite numerous clinical trials, improvements in the systemic treatment of this disease have been limited. Gemcitabine, a nucleoside [...] Read more.
Pancreatic cancer is one of the most lethal cancers, where curative surgical resections are rare and less than 5% of patients experience long-term survival. Despite numerous clinical trials, improvements in the systemic treatment of this disease have been limited. Gemcitabine, a nucleoside analogue, is still considered the standard of care chemotherapy for most patients in the advanced disease setting. To exert its cytotoxic effects, gemcitabine must enter cells via nucleoside transporters, most notably human equilibrative nucleoside transporter 1 (hENT1). Increasingly strong evidence suggests hENT1 is a prognostic biomarker in gemcitabine-treated pancreatic cancer, and may well be a predictive biomarker of gemcitabine efficacy. In this review, we synthesize the literature surrounding hENT1 in pancreatic cancer, identify the key outstanding questions, and suggest strategies to prospectively evaluate the clinical utility of hENT1 in future clinical studies. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
Open AccessReview Epithelial-Mesenchymal Transition in Pancreatic Carcinoma
Cancers 2010, 2(4), 2058-2083; doi:10.3390/cancers2042058
Received: 9 November 2010 / Revised: 1 December 2010 / Accepted: 1 December 2010 / Published: 9 December 2010
Cited by 22 | PDF Full-text (454 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic carcinoma is the fourth-leading cause of cancer death and is characterized by early invasion and metastasis. The developmental program of epithelial-mesenchymal transition (EMT) is of potential importance for this rapid tumor progression. During EMT, tumor cells lose their epithelial characteristics and [...] Read more.
Pancreatic carcinoma is the fourth-leading cause of cancer death and is characterized by early invasion and metastasis. The developmental program of epithelial-mesenchymal transition (EMT) is of potential importance for this rapid tumor progression. During EMT, tumor cells lose their epithelial characteristics and gain properties of mesenchymal cells, such as enhanced motility and invasive features. This review will discuss recent findings pertinent to EMT in pancreatic carcinoma. Evidence for and molecular characteristics of EMT in pancreatic carcinoma will be outlined, as well as the connection of EMT to related topics, e.g., cancer stem cells and drug resistance. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
Open AccessReview Contribution of Epithelial-Mesenchymal Transition to Pancreatic Cancer Progression
Cancers 2010, 2(4), 2084-2097; doi:10.3390/cancers2042084
Received: 24 October 2010 / Revised: 1 December 2010 / Accepted: 1 December 2010 / Published: 9 December 2010
Cited by 5 | PDF Full-text (292 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies, with median survival of less than one year and overall five-year survival of less than 5%. There is increasing evidence demonstrating that epithelial-mesenchymal transition (EMT) contributes to pancreatic cancer metastasis and [...] Read more.
Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies, with median survival of less than one year and overall five-year survival of less than 5%. There is increasing evidence demonstrating that epithelial-mesenchymal transition (EMT) contributes to pancreatic cancer metastasis and to treatment resistance. In this review, we will examine the data demonstrating the role and regulation of EMT in pancreatic cancer progression, focusing particularly on the transcription factors and microRNAs involved in EMT. We will examine how EMT is involved in the generation and maintenance of stem cells, and the role of EMT in modulating resistance of PDAC cells to drug therapies. We will also identify putative EMT-targeting agents that may help to reduce the morbidity and mortality associated with pancreatic cancer. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
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Open AccessReview Treatment of Brain Metastasis from Lung Cancer
Cancers 2010, 2(4), 2100-2137; doi:10.3390/cancers2042100
Received: 9 October 2010 / Revised: 11 November 2010 / Accepted: 2 December 2010 / Published: 15 December 2010
Cited by 12 | PDF Full-text (235 KB) | HTML Full-text | XML Full-text
Abstract
Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, [...] Read more.
Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, functional performance status, age, and number of brain metastases. Patients with good prognosis may benefit from more aggressive treatment because of the potential for prolonged survival for some of them. In this review, we will comprehensively discuss the therapeutic options for treating brain metastases, which arise mostly from a lung cancer primary. In particular, we will focus on the patient selection for combined modality treatment of brain metastases, such as surgical resection or stereotactic radiosurgery (SRS) combined with whole brain irradiation; the use of radiosensitizers; and the neurocognitive deficits after whole brain irradiation with or without SRS. The benefit of prophylactic cranial irradiation (PCI) and its potentially associated neuro-toxicity for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are also discussed, along with the combined treatment of intrathoracic primary disease and solitary brain metastasis. The roles of SRS to the surgical bed, fractionated stereotactic radiotherapy, WBRT with an integrated boost to the gross brain metastases, as well as combining WBRT with epidermal growth factor receptor (EGFR) inhibitors, are explored as well. Full article
(This article belongs to the Special Issue Organ-Specific Metastasis Formation)
Open AccessReview Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness
Cancers 2010, 2(4), 2138-2152; doi:10.3390/cancers2042138
Received: 1 November 2010 / Revised: 7 December 2010 / Accepted: 13 December 2010 / Published: 16 December 2010
Cited by 14 | PDF Full-text (375 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease [...] Read more.
Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis. Full article
(This article belongs to the Special Issue Pancreatic Cancer)
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Open AccessCommentary Commentary on Pancreatic Carcinoma: The Role of Radiofrequency Ablation in Advanced Disease
Cancers 2010, 2(4), 2055-2057; doi:10.3390/cancers2042055
Received: 25 August 2010 / Accepted: 12 November 2010 / Published: 8 December 2010
Cited by 3 | PDF Full-text (82 KB) | HTML Full-text | XML Full-text
Abstract Some comments about the role of ablation techniques in the management of advanced pancreatic cancer as palliative procedure. Full article
Open AccessCommentary Does Ablation Technique Utilized in the Management of Unresectable Locally Advanced Pancreatic Adenocarcinoma?
Cancers 2010, 2(4), 2098-2099; doi:10.3390/cancers2042098
Received: 9 December 2010 / Accepted: 10 December 2010 / Published: 10 December 2010
PDF Full-text (65 KB) | HTML Full-text | XML Full-text
Abstract Radiofrequency ablation in the management of advanced pancreatic cancer should be no longer utilized in patients with locally advanced or metastatic pancreatic adenocarcinoma. Full article

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