Journal of Oncology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Role of the Crosstalk between Autophagy and Apoptosis in Cancer Wed, 05 Jun 2013 14:14:31 +0000 http://www.hindawi.com/journals/jo/2013/102735/ Autophagy and apoptosis are catabolic pathways essential for organismal homeostasis. Autophagy is normally a cell-survival pathway involving the degradation and recycling of obsolete, damaged, or harmful macromolecular assemblies; however, excess autophagy has been implicated in type II cell death. Apoptosis is the canonical programmed cell death pathway. Autophagy and apoptosis have now been shown to be interconnected by several molecular nodes of crosstalk, enabling the coordinate regulation of degradation by these pathways. Normally, autophagy and apoptosis are both tumor suppressor pathways. Autophagy fulfils this role as it facilitates the degradation of oncogenic molecules, preventing development of cancers, while apoptosis prevents the survival of cancer cells. Consequently, defective or inadequate levels of either autophagy or apoptosis can lead to cancer. However, autophagy appears to have a dual role in cancer, as it has now been shown that autophagy also facilitates the survival of tumor cells in stress conditions such as hypoxic or low-nutrition environments. Here we review the multiple molecular mechanisms of coordination of autophagy and apoptosis and the role of the proteins involved in this crosstalk in cancer. A comprehensive understanding of the interconnectivity of autophagy and apoptosis is essential for the development of effective cancer therapeutics. Minfei Su, Yang Mei, and Sangita Sinha Copyright © 2013 Minfei Su et al. All rights reserved. The Haiti Breast Cancer Initiative: Initial Findings and Analysis of Barriers-to-Care Delaying Patient Presentation Wed, 05 Jun 2013 10:14:12 +0000 http://www.hindawi.com/journals/jo/2013/206367/ Background. In Haiti, breast cancer patients present at such advanced stages that even modern therapies offer modest survival benefit. Identifying the personal, sociocultural, and economic barriers-to-care delaying patient presentation is crucial to controlling disease. Methods. Patients presenting to the Hôpital Bon Sauveur in Cange were prospectively accrued. Delay was defined as 12 weeks or longer from initial sign/symptom discovery to presentation, as durations greater than this cutoff correlate with reduced survival. A matched case-control analysis with multivariate logistic regression was used to identify factors predicting delay. Results. Of patients accrued, 90 (73%) reported symptom-presentation duration and formed the basis of this study: 52 patients presented within 12 weeks of symptoms, while 38 patients waited longer than 12 weeks. On logistic regression, lower education status (OR = 5.6, ), failure to initially recognize mass as important (OR = 13.0, ), and fear of treatment cost (OR = 8.3, ) were shown to independently predict delayed patient presentation. Conclusion. To reduce stage at presentation, future interventions must educate patients on the recognition of initial breast cancer signs and symptoms and address cost concerns by providing care free of charge and/or advertising that existing care is already free. Ketan Sharma, Ainhoa Costas, Ruth Damuse, Jean Hamiltong-Pierre, Jordan Pyda, Cecilia T. Ong, Lawrence N. Shulman, and John G. Meara Copyright © 2013 Ketan Sharma et al. All rights reserved. Parameters That May Be Used for Predicting Failure during Endoscopic Retrograde Cholangiopancreatography Mon, 03 Jun 2013 14:10:08 +0000 http://www.hindawi.com/journals/jo/2013/201681/ Aim. Endoscopic retrograde cholangiopancreatography (ERCP) is frequently used for the diagnosis and treatment of hepatic, biliary tract, and pancreatic disorders. However, failure during cannulation necessitates other interventions. The aim of this study was to establish parameters that can be used to predict failure during ERCP. Methods. A total of 5884 ERCP procedures performed on 5079 patients, between 1991 and 2006, were retrospectively evaluated. Results. Cannulation was possible in 4482 (88.2%) patients. For each one-year increase in age, the cannulation failure rate increased by 1.01-fold (). A history of previous hepatic biliary tract surgery caused the cannulation failure rate to decrease by 0.487-fold (). A tumor infiltrating the ampulla, the presence of pathology obstructing the gastrointestinal passage, and peptic ulcer increased the failure rate by 78-, 28-, and 3.47-fold, respectively (). Conclusions.Patient gender and duodenal diverticula do not influence the success of cannulation during ERCP. Billroth II and Roux-en-Y gastrojejunostomy surgeries, a benign or malignant obstruction of the gastrointestinal system, and duodenal ulcers decrease the cannulation success rate, whereas a history of previous hepatic biliary tract surgery increases it. Although all endoscopists had equal levels of experience, statistically significant differences were detected among them. Emre Balik, Tunc Eren, Metin Keskin, Sedat Ziyade, Turker Bulut, Yilmaz Buyukuncu, and Sumer Yamaner Copyright © 2013 Emre Balik et al. All rights reserved. Tissue Banking, Bioinformatics, and Electronic Medical Records: The Front-End Requirements for Personalized Medicine Thu, 30 May 2013 18:40:04 +0000 http://www.hindawi.com/journals/jo/2013/368751/ Personalized medicine promises patient-tailored treatments that enhance patient care and decrease overall treatment costs by focusing on genetics and “-omics” data obtained from patient biospecimens and records to guide therapy choices that generate good clinical outcomes. The approach relies on diagnostic and prognostic use of novel biomarkers discovered through combinations of tissue banking, bioinformatics, and electronic medical records (EMRs). The analytical power of bioinformatic platforms combined with patient clinical data from EMRs can reveal potential biomarkers and clinical phenotypes that allow researchers to develop experimental strategies using selected patient biospecimens stored in tissue banks. For cancer, high-quality biospecimens collected at diagnosis, first relapse, and various treatment stages provide crucial resources for study designs. To enlarge biospecimen collections, patient education regarding the value of specimen donation is vital. One approach for increasing consent is to offer publically available illustrations and game-like engagements demonstrating how wider sample availability facilitates development of novel therapies. The critical value of tissue bank samples, bioinformatics, and EMR in the early stages of the biomarker discovery process for personalized medicine is often overlooked. The data obtained also require cross-disciplinary collaborations to translate experimental results into clinical practice and diagnostic and prognostic use in personalized medicine. K. Stephen Suh, Sreeja Sarojini, Maher Youssif, Kip Nalley, Natasha Milinovikj, Fathi Elloumi, Steven Russell, Andrew Pecora, Elyssa Schecter, and Andre Goy Copyright © 2013 K. Stephen Suh et al. All rights reserved. Comment on “HAX1 Augments Cell Proliferation, Migration, Adhesion, and Invasion Induced by Urokinase-Type Plasminogen Activator Receptor” Wed, 22 May 2013 10:02:12 +0000 http://www.hindawi.com/journals/jo/2013/782327/ Alicja Trebinska, Ryszard Konopinski, and Ewa A. Grzybowska Copyright © 2013 Alicja Trebinska et al. All rights reserved. Tumor-Associated Macrophages in Glioma: Friend or Foe? Wed, 08 May 2013 17:45:55 +0000 http://www.hindawi.com/journals/jo/2013/486912/ Tumor-associated macrophages (TAMs) contribute substantially to the tumor mass of gliomas and have been shown to play a major role in the creation of a tumor microenvironment that promotes tumor progression. Shortcomings of attempts at antiglioma immunotherapy may result from a failure to adequately address these effects. Emerging evidence supports an independent categorization of glioma TAMs as alternatively activated M2-type macrophages, in contrast to classically activated proinflammatory M1-type macrophages. These M2-type macrophages exert glioma-supportive effects through reduced anti-tumor functions, increased expression of immunosuppressive mediators, and nonimmune tumor promotion through expression of trophic and invasion-facilitating substances. Much of our work has demonstrated these features of glioma TAMs, and together with the supporting literature will be reviewed here. Additionally, the dynamics of glioma cell-TAM interaction over the course of tumor development remain poorly understood; our efforts to elucidate glioma cell-TAM dynamics are summarized. Finally, the molecular pathways which underlie M2-type TAM polarization and gene expression similarly require further investigation, and may present the most potent targets for immunotherapeutic intervention. Highlighting recent evidence implicating the transcription factor STAT3 in immunosuppressive tumorigenic glioma TAMs, we advocate for gene array-based approaches to identify yet unappreciated expression regulators and effector molecules important to M2-type glioma TAMs polarization and function within the glioma tumor microenvironment. Benjamin C. Kennedy, Christopher R. Showers, David E. Anderson, Lisa Anderson, Peter Canoll, Jeffrey N. Bruce, and Richard C. E. Anderson Copyright © 2013 Benjamin C. Kennedy et al. All rights reserved. Predictive Factors of Response in HER2-Positive Breast Cancer Treated by Neoadjuvant Therapy Mon, 29 Apr 2013 16:01:30 +0000 http://www.hindawi.com/journals/jo/2013/854121/ Since 2005, major progresses have been made in the neoadjuvant treatment of HER2-positive breast cancer. Trastuzumab introduction associated with chemotherapy has been the first major step leading to the improvement of the complete pathological response rate and, like in the adjuvant studies, better survivals. Dual HER2 blockade has been the next step and trastuzumab is associated now with other anti-HER2 therapies like lapatinib or pertuzumab, the latter being much more easy to use in combination with chemotherapy. Additional knowledge is necessary to better define within the HER2 tumor subgroup which patients could benefit more from targeted therapies. Different biomarkers have been studied to predict the response after anti-HER2 neoadjuvant therapies but until now none has been validated. S. Guiu, M. A. Mouret Reynier, M. Toure, and B. Coudert Copyright © 2013 S. Guiu et al. All rights reserved. Circulating Prostate Cells Found in Men with Benign Prostate Disease Are P504S Negative: Clinical Implications Wed, 17 Apr 2013 13:13:36 +0000 http://www.hindawi.com/journals/jo/2013/165014/ Introduction. Developments in immunological and quantitative real-time PCR-based analysis have enabled the detection, enumeration, and characterization of circulating tumor cells (CTCs). It is assumed that the detection of CTCs is associated with cancer, based on the finding that CTCs can be detected in all major cancer and not in healthy subjects or those with benign disease. Methods and Patients. Consecutive men, with suspicion of prostate cancer, had blood samples taken before prostate biopsy; mononuclear cells were obtained using differential gel centrifugation and CPCs detecting using anti-PSA immunocytochemistry. Positive samples underwent further classification with anti-P504S. Results. 329 men underwent prostate biopsy; of these men 83 underwent a second biopsy and 44 a third one. Of those with a biopsy negative for cancer, 19/226 (8.4%) had CPCs PSA (+) P504S (−) detected at first biopsy, 6/74 (8.1%) at second biopsy, and 5/33 (15.2%) at third biopsy. Men with cancer-positive biopsies did not have PSA (+) P504S (−) CPCs detected. These benign cells were associated with chronic prostatitis. Conclusions. Patients with chronic prostatitis may have circulating prostate cells detected in blood, which do not express the enzyme P504S and should be thought of as benign in nature. Nigel P. Murray, Eduardo Reyes, Leonardo Badínez, Nelson Orellana, Cynthia Fuentealba, Ruben Olivares, José Porcell, and Ricardo Dueñas Copyright © 2013 Nigel P. Murray et al. All rights reserved. Safety and Efficacy of Radiofrequency Ablation in the Management of Unresectable Bile Duct and Pancreatic Cancer: A Novel Palliation Technique Mon, 08 Apr 2013 15:46:10 +0000 http://www.hindawi.com/journals/jo/2013/910897/ Objectives. Radiofrequency ablation (RFA) has replaced photodynamic therapy for premalignant and malignant lesions of the esophagus. However, there is limited experience in the bile duct. The objective of this pilot study was to assess the safety and efficacy of RFA in malignant biliary strictures. Methods: Twenty patients with unresectable malignant biliary strictures underwent RFA with stenting between June 2010 and July 2012. Diameters of the stricture before and after RFA, immediate and 30 day complications and stent patency were recorded prospectively. Results. A total of 25 strictures were treated. Mean stricture length treated was 15.2 mm (SD = 8.7 mm, Range = 3.5–33 mm). Mean stricture diameter before RFA was 1.7 mm (SD = 0.9 mm, Range = 0.5–3.4 mm) while the mean diameter after RFA was 5.2 mm (SD = 2 mm, Range = 2.6–9 mm). There was a significant increase of 3.5 mm (t = 10.8, DF = 24, P value = <.0001) in the bile duct diameter post RFA. Five patients presented with pain after the procedure, but only one developed mild post-ERCP pancreatitis and cholecystitis. Conclusions: Radiofrequency ablation can be a safe palliation option for unresectable malignant biliary strictures. A multicenter randomized controlled trial is required to confirm the long term benefits of RFA and stenting compared to stenting alone. Paola Figueroa-Barojas, Mihir R. Bakhru, Nagy A. Habib, Kristi Ellen, Jennifer Millman, Armeen Jamal-Kabani, Monica Gaidhane, and Michel Kahaleh Copyright © 2013 Paola Figueroa-Barojas et al. All rights reserved. Progress in Using Circulating Tumor Cell Information to Improve Metastatic Breast Cancer Therapy Mon, 25 Mar 2013 16:07:45 +0000 http://www.hindawi.com/journals/jo/2013/702732/ Circulating tumor cells (CTCs) were discovered nearly 150 years ago but have only recently been recognized as a feature of most solid tumors due to their extremely low concentration in the peripheral circulation. Several technologies have been developed to isolate and analyze CTCs, which can now be routinely accessed for clinical information. The most mature of these (the CELLSEARCH system) uses immunomagnetic selection of epithelial cell adhesion molecule to isolate CTCs for analysis. Studies using this system have demonstrated that categorization of patients into high and low CTC groups using a validated decision point is prognostic in patients with metastatic breast, colorectal, or prostate cancer. Initial attempts to use CTC counts to guide therapeutic decisions appeared to yield positive results and key concepts in clinical application of CTC information, including the CTC cutoff, predictive value in disease subtypes, and comparison to current evaluation methods, have been demonstrated. Clinical studies of the impact of CTC counts in routine clinical practice are ongoing; however, recent published evidence on the clinical use of CTCs in metastatic breast cancer continues to support these concepts, and experience in the community oncology setting also suggests that CTC enumeration can be useful for therapy management. Jose Alemar and Eric R. Schuur Copyright © 2013 Jose Alemar and Eric R. Schuur. All rights reserved. Analysis of the mRNA Expression of Chemotherapy-Related Genes in Colorectal Carcinoma Using the Danenberg Tumor Profile Method Sat, 16 Mar 2013 15:02:56 +0000 http://www.hindawi.com/journals/jo/2013/386906/ The establishment of individualized chemotherapy for colorectal carcinoma based on the expression of genes involved in chemotherapeutic sensitivity or prognosis is necessary. To achieve this, the expression profiles of genes within tumors and their relationship to clinicopathological factors must be elucidated. Here, we selected 10 genes (TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, TOPO-1, VEGF, and EGFR), examined differences in their mRNA expression between the upper and lower thirds of tumors by laser-captured microdissection and real-time RT-PCR (the Danenberg tumor profile), and analyzed the relationships between their expression profiles and clinicopathological factors. Interestingly, the mRNA expression of DPD, TP, and VEGF was significantly higher in the lower third than in the upper third of tumors (, , and , resp.). Furthermore, increased ERCC1 mRNA expression in the lower third of tumors correlated with recurrence (), and VEGF mRNA expression was significantly higher in cases with recurrence than in cases without recurrence, both in the upper and lower thirds of tumors ( and , resp.). These results implied that heterogeneity in DPD, TP, and VEGF expression may exist in colorectal carcinoma and that ERCC-1 and VEGF may be markers predicting recurrence after curative operation. Shin Sasaki, Toshiyuki Watanabe, and Hiroshi Nakayama Copyright © 2013 Shin Sasaki et al. All rights reserved. Protumor Activities of the Immune Response: Insights in the Mechanisms of Immunological Shift, Oncotraining, and Oncopromotion Thu, 14 Mar 2013 15:11:35 +0000 http://www.hindawi.com/journals/jo/2013/835956/ Experimental and clinical studies indicate that cells of the innate and adaptive immune system have both anti- and pro-tumor activities. This dual role of the immune system has led to a conceptual shift in the role of the immune system’s regulation of cancer, in which immune-tumor cell interactions are understood as a dynamic process that comprises at least five phases: immunosurveillance, immunoselection, immunoescape, oncotraining, and oncopromotion. The tumor microenvironment shifts immune cells to perform functions more in tune with the tumor needs (oncotraining); these functions are related to chronic inflammation and tissue remodeling activities. Among them are increased proliferation and survival, increased angiogenesis and vessel permeability, protease secretion, acquisition of migratory mesenchymal characteristics, and self-renewal properties that altogether promote tumor growth and metastasis (oncopromotion). Important populations in all these pro-tumor processes are M2 macrophages, N2 neutrophils, regulatory T cells, and myeloid derived suppressor cells; the main effectors molecules are CSF-1, IL-6, metalloproteases, VEGF, PGE-2, TGF-β, and IL-10. Cancer prognosis correlates with densities and concentrations of protumoral populations and molecules, providing ideal targets for the intelligent design of directed preventive or anticancer therapies. G. K. Chimal-Ramírez, N. A. Espinoza-Sánchez, and E. M. Fuentes-Pananá Copyright © 2013 G. K. Chimal-Ramírez et al. All rights reserved. A Clinical Update and Radiologic Review of Pediatric Orbital and Ocular Tumors Tue, 12 Mar 2013 15:44:58 +0000 http://www.hindawi.com/journals/jo/2013/975908/ While pediatric orbital tumors are most often managed in tertiary care centers, clinicians should be aware of the signs of intraocular and orbital neoplasms. In the pediatric population, a delay in diagnosis of orbital and intraocular lesions, even if benign, can lead to vision loss and deformity. Intraocular lesions reviewed are retinoblastoma, medulloepithelioma, and retinal astrocytic hamartoma. Orbital neoplasms reviewed are rhabdomyosarcoma, neuroblastoma metastases, optic pathway glioma, plexiform neurofibroma, leukemia, lymphoprolipherative disease, orbital inflammatory syndrome, dermoid and epidermoid inclusion cysts, and Langerhans’ cell histiocytosis. Vascular lesions reviewed are infantile hemangioma and venous lymphatic malformation. In conjunction with clinical examination, high-resolution ophthalmic imaging and radiologic imaging play an important role in making a diagnosis and differentiating between benign and likely malignant processes. The radiologic imaging characteristics of these lesions will be discussed to facilitate prompt diagnosis and treatment. The current treatment modalities and management of tumors will also be reviewed. Ajay A. Rao, John H. Naheedy, James Y.-Y. Chen, Shira L. Robbins, and Hema L. Ramkumar Copyright © 2013 Ajay A. Rao et al. All rights reserved. Subsite-Specific Dietary Risk Factors for Colorectal Cancer: A Review of Cohort Studies Tue, 12 Mar 2013 09:12:06 +0000 http://www.hindawi.com/journals/jo/2013/703854/ Objective. A shift in the total incidence from left- to right-sided colon cancer has been reported and raises the question as to whether lifestyle risk factors are responsible for the changing subsite distribution of colon cancer. The present study provides a review of the subsite-specific risk estimates for the dietary components presently regarded as convincing or probable risk factors for colorectal cancer: red meat, processed meat, fiber, garlic, milk, calcium, and alcohol. Methods. Studies were identified by searching PubMed through October 8, 2012 and by reviewing reference lists. Thirty-two prospective cohort studies are included, and the estimates are compared by sex for each risk factor. Results. For alcohol, there seems to be a stronger association with rectal cancer than with colon cancer, and for meat a somewhat stronger association with distal colon and rectal cancer, relative to proximal colon cancer. For fiber, milk, and calcium, there were only minor differences in relative risk across subsites. No statement could be given regarding garlic. Overall, many of the subsite-specific risk estimates were nonsignificant, irrespective of exposure. Conclusion. For some dietary components the associations with risk of cancer of the rectum and distal colon appear stronger than for proximal colon, but not for all. Anette Hjartåker, Bjarte Aagnes, Trude Eid Robsahm, Hilde Langseth, Freddie Bray, and Inger Kristin Larsen Copyright © 2013 Anette Hjartåker et al. All rights reserved. Detection of Immunoglobulin G against E7 of Human Papillomavirus in Non-Small-Cell Lung Cancer Sun, 03 Mar 2013 16:25:57 +0000 http://www.hindawi.com/journals/jo/2013/240164/ Background. A significant number of non-small-cell lung cancers (NSCLC) have human papillomavirus (HPV) DNA integrated in their genome. This study sought to further establish HPV’s possible etiologic link to NSCLC by evaluating an immune response to HPV’s oncogene, E7, in patients with NSCLC. Patients and Methods. Antibodies (IgG) in serum against E7 for HPV 16 and 18 in 100 patients with NSCLC were examined by enzyme-linked immunosorbent assay (ELISA). Results. Sixteen NSCLC patients were found to have a high titration of IgG for HPV oncogenic E7 protein. 23.5% of adenocarcinomas (AC,) and 15.4% of squamous cell carcinomas (SCC) were positive for IgG against HPV E7. HPV-18 (11%) had a slightly higher frequency than HPV-16 (6%). Of the six positive cases for HPV-16, 3 were AC, 2 SCC, and 1 NOS (not otherwise specified). For the 11 HPV-18 positives, 7 were AC, and 4 SCC. The one case with IgG against HPV 16 and 18 was AC. One case had high cross-reactive levels against E7 of HPV 16 and 18. Two (28%) of 7 patients who reported never smoking were positive for HPV, and 12 (13.6%) of 88 smokers were HPV positive. Conclusions. The study detected high levels of IgG against E7 in 16% of NSCLC patients. This adds evidence to a potential role of HPV in the pathogenesis of NSCLC. Raul Storey, Joongho Joh, Amy Kwon, A. Bennett Jenson, Shin-je Ghim, and Goetz H. Kloecker Copyright © 2013 Raul Storey et al. All rights reserved. Mammalian Target of Rapamycin Inhibitors Induce Tumor Cell Apoptosis In Vivo Primarily by Inhibiting VEGF Expression and Angiogenesis Thu, 28 Feb 2013 14:08:56 +0000 http://www.hindawi.com/journals/jo/2013/897025/ We found that rapalog mTOR inhibitors induce G1 arrest in the PTEN-null HS Sultan B-cell lymphoma line in vitro, but that administration of rapalogs in a HS Sultan xenograft model resulted in significant apoptosis, and that this correlated with induction of hypoxia and inhibition of neoangiogenesis and VEGF expression. Mechanistically, rapalogs prevent cap-dependent translation, but studies have shown that cap-independent, internal ribosome entry site (IRES)-mediated translation of genes, such as c-myc and cyclin D, can provide a fail-safe mechanism that regulates tumor survival. Therefore, we tested if IRES-dependent expression of VEGF could likewise regulate sensitivity of tumor cells in vivo. To achieve this, we developed isogenic HS Sultan cell lines that ectopically express the VEGF ORF fused to the p27 IRES, an IRES sequence that is insensitive to AKT-mediated inhibition of IRES activity and effective in PTEN-null tumors. Mice challenged with p27-VEGF transfected tumor cells were more resistant to the antiangiogenic and apoptotic effects of the rapalog, temsirolimus, and active site mTOR inhibitor, pp242. Our results confirm the critical role of VEGF expression in tumors during treatment with mTOR inhibitors and underscore the importance of IRES activity as a resistance mechanism to such targeted therapy. Patrick Frost, Eileen Berlanger, Veena Mysore, Bao Hoang, YiJiang Shi, Joseph Gera, and Alan Lichtenstein Copyright © 2013 Patrick Frost et al. All rights reserved. Prevalence of Human Papillomavirus in 45 Greek Patients with Oral Cancer Wed, 27 Feb 2013 08:36:54 +0000 http://www.hindawi.com/journals/jo/2013/756510/ The relation between HPV and head and neck cancer has recently and extensively been investigated. The purpose of this study was to indentify HPV genotypes, as well as E6/E7 mRNA expression of high-risk HPVs (16, 18, 31, 33 and 45) in oral squamous cell carcinomas (OSCCs) from 45 Greek patients. The overall prevalence of HPV DNA positive OSCCs was 11.1% (5/45), while high-risk HPV DNA was found in 6.7% (3/45) of OSCCs. E6/E7 mRNA expression was detected in 8.9% (4/45) of the oral cavity samples. Our data indicated that HPV 16 was the commonest genotype identified in HPV-positive OSCCs by both DNA and RNA tests. This study confirms the prevalence of HPV infections among patients with OSCCs. Future analysis and followup of more OSCCs will enable us to correlate HPV detection and clinical outcome. Maria Kouvousi, Dimitra Xesfyngi, Elpida Tsimplaki, Elena Argyri, Georgia Ioannidou, Maria Ploxorou, Andreas C. Lazaris, Efstratios Patsouris, and Efstathia Panotopoulou Copyright © 2013 Maria Kouvousi et al. All rights reserved. Enhancement of Cisplatin-Mediated Apoptosis in Ovarian Cancer Cells through Potentiating G2/M Arrest and p21 Upregulation by Combinatorial Epigallocatechin Gallate and Sulforaphane Sun, 17 Feb 2013 11:05:07 +0000 http://www.hindawi.com/journals/jo/2013/872957/ Advanced-stage ovarian cancer is characterized by high mortality due to development of resistance to conventional chemotherapy. Novel compounds that can enhance the efficacy of conventional chemotherapy in ovarian cancer may overcome this drug resistance. Consumption of green tea (epigallocatechin gallate, EGCG) and cruciferous vegetables (sulforaphane, SFN) is inversely associated with occurrence of ovarian cancer and has anticancer effects through targeting multiple molecules in cancer cells. However, the effects of EGCG and SFN combinational treatment on ovarian cancer cells and on efficacy of cisplatin to these cells are unknown. In this study, EGCG or SFN was used to treat both cisplatin-sensitive (A2780) and cisplatin-resistant (A2780/CP20) ovarian cancer cells alone or in combination with cisplatin. We found that EGCG and SFN combinational treatment can reduce cell viability of both ovarian cancer cell lines time- and dose-dependently. Furthermore, EGCG and SFN combinational treatment can enhance cisplatin-induced apoptosis and G2/M phase arrest, thereby enhancing the efficacy of cisplatin on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. EGCG and SFN combinational treatment upregulated p21 expression induced by cisplatin in cisplatin-sensitive ovarian cancer cells, while p27 expression was not regulated by these treatments. Collectively, these studies provide novel approaches to overcoming cisplatin chemotherapy resistance in ovarian cancer. Huaping Chen, Charles N. Landen, Yuanyuan Li, Ronald D. Alvarez, and Trygve O. Tollefsbol Copyright © 2013 Huaping Chen et al. All rights reserved. Which Imaging Modality Is Superior for Prediction of Response to Neoadjuvant Chemotherapy in Patients with Triple Negative Breast Cancer? Mon, 11 Feb 2013 15:52:36 +0000 http://www.hindawi.com/journals/jo/2013/964863/ Background and Objectives. Triple negative breast cancer (TNBC) has been shown to be generally chemosensitive. We sought to investigate the utility of mammography (MMG), ultrasonography (US), and breast magnetic resonance imaging (MRI) in predicting residual disease following neoadjuvant chemotherapy for TNBC. Methods. We identified 148 patients with 151 Stage I–III TNBC treated with neoadjuvant chemotherapy. Residual tumor size was estimated by MMG, US, and/or MRI prior to surgical intervention and compared to the subsequent pathologic residual tumor size. Data were compared using chi-squared test. Results. Of 151 tumors, 44 (29%) did not have imaging performed prior to surgical treatment. Thirty-eight (25%) tumors underwent a pathologic complete response (pCR), while 113 (75%) had residual invasive disease. The imaging modality was accurate to within 1 cm of the final pathologic residual disease in 74 (69%) cases and within 2 cm in 94 (88%) cases. Groups were similar with regards to patient age, race, tumor size and grade, and clinical stage (). Accuracy to within 1 cm was the highest for US (83%) and the lowest for MMG (56%) (). Conclusions. Breast US and MRI were more accurate than MMG in predicting residual tumor size following neoadjuvant chemotherapy in patients with TNBC. None of the imaging modalities were predictive of a pCR. Jordan J. Atkins, Catherine M. Appleton, Carla S. Fisher, Feng Gao, and Julie A. Margenthaler Copyright © 2013 Jordan J. Atkins et al. All rights reserved. Role of Obesity in the Risk of Breast Cancer: Lessons from Anthropometry Sun, 03 Feb 2013 18:00:16 +0000 http://www.hindawi.com/journals/jo/2013/906495/ An estimated 1.38 million new cases of breast cancer (BC) are diagnosed each year in women worldwide. Of these, the majority are categorized as invasive ductal cell carcinoma. Subgroups of BC are frequently distinguished into five “intrinsic” subtypes, namely, luminal A, luminal B, normal-like, HER2-positive, and basal-like subtypes. Epidemiological evidence has shown that anthropometric factors are implicated in BC development. Overall consistent positive associations have been observed between high body mass index (BMI) and waist-to-hip ratio (WHR) and the risk of BC among postmenopausal women, while conflicting results persist for premenopausal BC, both for BMI and for other anthropometric parameters as well as across ethnic groups. Furthermore, some evidence suggests that body size, body shape, and weight gain during childhood or adolescence may play a role in the risk of BC. In this paper, we describe the evidence linking anthropometric indices at different ages and BC risk, in order to improve our understanding of the role of body fat distribution in the risk of BC, investigate differences in these associations according to menopausal status and ethnic groups, and discuss the potential biological mechanisms linking body size and BC risk. Amina Amadou, Pierre Hainaut, and Isabelle Romieu Copyright © 2013 Amina Amadou et al. All rights reserved. The Use of Strontium-90 Beta Radiotherapy as Adjuvant Treatment for Conjunctival Melanoma Thu, 31 Jan 2013 10:22:30 +0000 http://www.hindawi.com/journals/jo/2013/349162/ Background/Aims. To report the safety and efficacy of strontium (Sr90) beta radiotherapy as adjuvant treatment for conjunctival melanoma. Methods. A retrospective cohort study was undertaken from 1999 to 2007 of all patients who underwent Sr90 beta radiotherapy for incompletely excised conjunctival melanoma. Failure of treatment was defined as recurrence of a conjunctival melanoma at the same location following beta radiotherapy. Results. Twenty patients underwent Sr90 beta radiotherapy for incompletely excised conjunctival melanoma. Median follow-up interval was 59 months (8–152). All patients had conjunctival melanoma involving the bulbar conjunctiva. Underlying diagnoses included PAM with atypia in 60% (12 of 20), PAM without atypia in 15% (3 of 20), and de novo conjunctival melanoma in 25% (5 of 20). Following Sr90 beta radiotherapy, in 90% (18 out of 20) local control was achieved and visual acuity was not affected in any patient. Three patients (15%) had dry eye symptoms, episcleritis, and descemetcoele, respectively. No cataract or secondary glaucoma was reported. Conclusions. Sr90 treatment is a very effective adjuvant treatment after excisional biopsy and cryotherapy for conjunctival melanoma with a local success rate of 90%. The treatment is not associated with significant side effects and visual acuity is not affected. Victoria M. L. Cohen, Vasilios P. Papastefanou, S. Liu, Ian Stoker, and John L. Hungerford Copyright © 2013 Victoria M. L. Cohen et al. All rights reserved. Multiple Myeloma Macrophages: Pivotal Players in the Tumor Microenvironment Wed, 30 Jan 2013 08:57:55 +0000 http://www.hindawi.com/journals/jo/2013/183602/ Tumor microenvironment is essential for multiple myeloma (MM) growth, progression, and drug resistance through provision of survival signals and secretion of growth and proangiogenic factors. This paper examines the importance of macrophages within MM bone marrow (BM) microenvironment, referred to as MM-associated macrophages, as a potential niche component that supports tumor plasma cells. These macrophages are derived from peripheral blood monocytes recruited into the tumor. Upon activation by MM plasma cells and mesenchymal stromal cells, macrophages can release growth factors, proteolytic enzymes, cytokines, and inflammatory mediators that promote plasma cell growth and survival. Macrophages promote tumor progression through several mechanisms including angiogenesis, growth, and drug resistance. Indeed, these macrophages are essential for the induction of an angiogenic response through vasculogenic mimicry, and this ability proceeds in step with progression of the plasma cell tumors. Data suggest that macrophages play an important role in the biology and survival of patients with MM, and they may be a target for the MM antivascular management. Simona Berardi, Roberto Ria, Antonia Reale, Annunziata De Luisi, Ivana Catacchio, Michele Moschetta, and Angelo Vacca Copyright © 2013 Simona Berardi et al. All rights reserved. Metastasis: Genetics, Mechanism, and Diagnostic and Therapeutic Strategies Sun, 30 Dec 2012 10:42:18 +0000 http://www.hindawi.com/journals/jo/2012/390835/ Mehmet Gunduz, Esra Gunduz, Levent Beder, Davut Pehlivan, Omer Faruk Hatipoglu, Sushant Kachhap, and Reidar Grenman Copyright © 2012 Mehmet Gunduz et al. All rights reserved. Molecular Imaging in Breast Cancer Sat, 29 Dec 2012 18:22:39 +0000 http://www.hindawi.com/journals/jo/2012/426260/ Alvaro Ruibal, José María Benlloch, Renato Valdés Olmos, and Bengt Langstrom Copyright © 2012 Alvaro Ruibal et al. All rights reserved. Recent Design Development in Molecular Imaging for Breast Cancer Detection Using Nanometer CMOS Based Sensors Mon, 24 Dec 2012 11:37:08 +0000 http://www.hindawi.com/journals/jo/2012/680262/ As one of the key clinical imaging methods, the computed X-ray tomography can be further improved using new nanometer CMOS sensors. This will enhance the current technique's ability in terms of cancer detection size, position, and detection accuracy on the anatomical structures. The current paper reviewed designs of SOI-based CMOS sensors and their architectural design in mammography systems. Based on the existing experimental results, using the SOI technology can provide a low-noise (SNR around 87.8 db) and high-gain (30 v/v) CMOS imager. It is also expected that, together with the fast data acquisition designs, the new type of imagers may play important roles in the near-future high-dimensional images in additional to today's 2D imagers. Dung C. Nguyen, Dongsheng (Brian) Ma, and Janet M. W. Roveda Copyright © 2012 Dung C. Nguyen et al. All rights reserved. Fatty Acids in Habitual Diet, Plasma Phospholipids, and Tumour and Normal Colonic Biopsies in Young Colorectal Cancer Patients Sun, 23 Dec 2012 14:39:03 +0000 http://www.hindawi.com/journals/jo/2012/254801/ Fatty acid metabolism is altered in colorectal cancer (CRC). We aimed to investigate incorporation of dietary -6 and -3 polyunsaturated fatty acids (PUFAs) into plasma phospholipids (PLs), tumour tissue, and normal mucosa in young CRC patients. We also aimed to study differences in PUFA composition between tumour and normal mucosa, and PUFA status associated with cancer stage. Sixty-five CRC patients younger than 55 years were included in a multicenter study. We assessed dietary fatty acid composition by food-frequency questionnaire. Fatty acid composition in plasma PL () and tumour and normal colonic biopsies () were analysed by gas chromatography. We observed a significant correlation for docosahexaenoic acid (DHA) between dietary intake and concentration in plasma PL (weight%) (; ), but not for any -6 PUFA. Tissue concentrations of arachidonic acid, eicosapentaenoic acid, and DHA (weight%) were 1.7–2.5 times higher in tumour than normal mucosa (). Concentrations of -3 and -6 PUFA in plasma PL and tissues were not related to Duke's stage, although patients with more severe cancer stage reported higher intake of -3 PUFA. In conclusion, we found accumulation of the long-chained -3 and -6 PUFA in tumour tissue in young CRC patients. Paula Berstad, Espen Thiis-Evensen, Morten H. Vatn, and Kari Almendingen Copyright © 2012 Paula Berstad et al. All rights reserved. Early Detection Biomarkers for Ovarian Cancer Sun, 23 Dec 2012 13:16:52 +0000 http://www.hindawi.com/journals/jo/2012/709049/ Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultrasonography, biomarker analysis, or a combination of both. In this paper we review recent research on novel and robust biomarkers for early detection of ovarian cancer and provide specific details on their contributions to tumorigenesis. Promising biomarkers for early detection of ovarian cancer include KLK6/7, GSTT1, PRSS8, FOLR1, ALDH1, and miRNAs. Sreeja Sarojini, Ayala Tamir, Heejin Lim, Shihong Li, Shifang Zhang, Andre Goy, Andrew Pecora, and K. Stephen Suh Copyright © 2012 Sreeja Sarojini et al. All rights reserved. Dietary Agents in Cancer Chemoprevention and Treatment Tue, 18 Dec 2012 08:31:20 +0000 http://www.hindawi.com/journals/jo/2012/749310/ Julian J. Raffoul, Omer Kucuk, Fazlul H. Sarkar, and Gilda G. Hillman Copyright © 2012 Julian J. Raffoul et al. All rights reserved. New Perspectives on Diagnostics, Prognosis, and Therapy in Aggressive Endocrine Tumours Wed, 05 Dec 2012 09:18:16 +0000 http://www.hindawi.com/journals/jo/2012/820938/ Marialuisa Appetecchia, Bruce H. R. Wolffenbuttel, and Saadi Al Jadir Copyright © 2012 Marialuisa Appetecchia et al. All rights reserved. Optical Imaging in Breast Cancer Diagnosis: The Next Evolution Tue, 04 Dec 2012 10:53:40 +0000 http://www.hindawi.com/journals/jo/2012/863747/ Breast cancer is one of the most common cancers among the population of the Western world. Diagnostic methods include mammography, ultrasound, and magnetic resonance; meanwhile, nuclear medicine techniques have a secondary role, being useful in regional assessment and therapy followup. Optical imaging is a very promising imaging technique that uses near-infrared light to assess optical properties of tissues and is expected to play an important role in breast cancer detection. Optical breast imaging can be performed by intrinsic breast tissue contrast alone (hemoglobin, water, and lipid content) or with the use of exogenous fluorescent probes that target specific molecules for breast cancer. Major advantages of optical imaging are that it does not use any radioactive components, very high sensitivity, relatively inexpensive, easily accessible, and the potential to be combined in a multimodal approach with other technologies such as mammography, ultrasound, MRI, and positron emission tomography. Moreover, optical imaging agents could, potentially, be used as “theranostics,” combining the process of diagnosis and therapy. Michel Herranz and Alvaro Ruibal Copyright © 2012 Michel Herranz and Alvaro Ruibal. All rights reserved.