Journal of Oncology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Phosphoglycerate Dehydrogenase: Potential Therapeutic Target and Putative Metabolic Oncogene Tue, 09 Dec 2014 08:56:12 +0000 Exemplified by cancer cells’ preference for glycolysis, for example, the Warburg effect, altered metabolism in tumorigenesis has emerged as an important aspect of cancer in the past 10–20 years. Whether due to changes in regulatory tumor suppressors/oncogenes or by acting as metabolic oncogenes themselves, enzymes involved in the complex network of metabolic pathways are being studied to understand their role and assess their utility as therapeutic targets. Conversion of glycolytic intermediate 3-phosphoglycerate into phosphohydroxypyruvate by the enzyme phosphoglycerate dehydrogenase (PHGDH)—a rate-limiting step in the conversion of 3-phosphoglycerate to serine—represents one such mechanism. Forgotten since classic animal studies in the 1980s, the role of PHGDH as a potential therapeutic target and putative metabolic oncogene has recently reemerged following publication of two prominent papers near-simultaneously in 2011. Since that time, numerous studies and a host of metabolic explanations have been put forward in an attempt to understand the results observed. In this paper, I review the historic progression of our understanding of the role of PHGDH in cancer from the early work by Snell through its reemergence and rise to prominence, culminating in an assessment of subsequent work and what it means for the future of PHGDH. Cheryl K. Zogg Copyright © 2014 Cheryl K. Zogg. All rights reserved. Absence of HPV Infection Is Associated with Smoker Patients with Squamous Cell Carcinoma of the Oropharynx Tue, 30 Sep 2014 11:12:57 +0000 The purpose of this study was to evaluate the survival of patients with SCC of the oropharynx, according to the presence of HPV and tobacco consumption. A total of 37 patients were followed up for at least 5 years after being diagnosed with SCC of the oropharynx. The biopsy tissue was submitted to the polymerase chain reaction (PCR) and in situ hybridization (ISH) methods for broad determination of HPV presence, to identify the presence of high-risk viruses (16 and 18). 12 of the 37 (32.4%) samples were HPV positive, whereas the two specific types of virus were identified in two samples for HPV-16 and in no samples for HPV-18. We observed no significant effect of the virus in survival analysis, irrespective of tobacco consumption. The level of tobacco consumption was significantly higher in the group of HPV-negative patients (), in which all the patients in this group were smokers. Therefore, HPV did not change the survival of patients with SCC of the oropharynx in this study, indicating that factors other than tobacco need to be studied in conjunction with it, and the level of tobacco consumption is significantly higher in the group of HPV-negative patients. Gláucia Resende Soares, Adriana Demathé, Neivio José Mattar, Éder Ricardo Biasoli, and Glauco Issamu Miyahara Copyright © 2014 Gláucia Resende Soares et al. All rights reserved. Comparison of Short and Continuous Hydration Regimen in Chemotherapy Containing Intermediate- to High-Dose Cisplatin Wed, 24 Sep 2014 08:04:59 +0000 Aim. The efficacy of the short hydration regimen was reported in chemotherapy containing intermediate- to high-dose cisplatin, and the use of outpatient chemotherapy containing cisplatin with short hydration has been widespread in recent years. Methods. We compared patients with gastric cancer, lung cancer, and urothelial cancer who received outpatient chemotherapy containing cisplatin (≥60 mg/m2/cycle) with the short hydration regimen since April 2012 with those who received hospital chemotherapy with continuous hydration between April 2011 and March 2013 in our hospital. Results. Grade 2 or higher acute kidney injury occurred in 2 patients in the continuous hydration group and in no patient in the short hydration group; 1 patient discontinued treatment on account of nephrotoxicity. There was no difference between the 2 groups in maximum creatinine increment and maximum clearance decrement. Relative dose intensity in the short hydration group was higher than that in the continuous hydration group (89.5% versus 80.3%; ). Conclusions. The short hydration regimen in outpatient chemotherapy containing intermediate- to high-dose cisplatin is as safe as the continuous hydration regimen and increased the efficacy of chemotherapy. Akira Ouchi, Masahiko Asano, Keiya Aono, Tetsuya Watanabe, and Takehiro Kato Copyright © 2014 Akira Ouchi et al. All rights reserved. Development of a Score Predicting Survival after Palliative Reirradiation Sun, 21 Sep 2014 09:40:00 +0000 Purpose. To develop a prognostic model for predicting survival after palliative reirradiation (PR). Methods and Materials. We analyzed all 87 PR courses administered at a dedicated palliative radiotherapy facility between 20.06.2007 (opening) and 31.12.2009. Uni- and multivariate survival analyses were performed, the previously published survival prediction score (SPS) was evaluated, and a PR-specific prognostic score was calculated. Results. In multivariate analysis, four parameters significantly influenced survival: performance status, use of steroids, presence of liver metastases, and pleural effusion. Based on these parameters, a 4-tiered score was developed. Median survival was 24.5 months for the favorable group, 9.7 and 2.8 months for the two intermediate groups, and 1.1 months for the unfavorable group ( for comparison between the two favorable groups and for all other pair-wise comparisons). All patients in the unfavorable group died within 2 months. Conclusion. The performance of PR-specific score was promising and might facilitate identification of patients who survive long enough to benefit from PR. It should be validated in independent patient groups, ideally from several institutions and countries. Carsten Nieder, Nicolaus Andratschke, Kent Angelo, Ellinor Haukland, and Anca L. Grosu Copyright © 2014 Carsten Nieder et al. All rights reserved. Genomically Driven Precision Medicine to Improve Outcomes in Anaplastic Thyroid Cancer Sun, 07 Sep 2014 08:48:57 +0000 Thyroid cancer is an endocrine malignancy with an incidence rate that has been increasing steadily over the past 30 years. While well-differentiated subtypes have a favorable prognosis when treated with surgical resection and radioiodine, undifferentiated subtypes, such as anaplastic thyroid cancer (ATC), are far more aggressive and have a poor prognosis. Conventional therapies (surgical resection, radiation, chemotherapy, and radioiodine) have been utilized for treatment of ATC, yet these treatments have not significantly improved the overall mortality rate. As cancer is a genetic disease, genetic alterations such as mutations, fusions, activation of oncogenes, and silencing of tumor suppressors contribute to its aggressiveness. With the use of next-generation sequencing and the Cancer Genome Atlas, mutation-directed therapy is recognized as the upcoming standard of care. In this review, we highlight the known genetic landscape of ATC and the need for a comprehensive genetic characterization of this disease in order to identify additional therapeutic targets to improve patient outcomes. Nicole Pinto, Morgan Black, Krupal Patel, John Yoo, Joe S. Mymryk, John W. Barrett, and Anthony C. Nichols Copyright © 2014 Nicole Pinto et al. All rights reserved. Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer Mon, 01 Sep 2014 07:12:46 +0000 Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease () and complete response to platinum-based chemotherapy () occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer ( months) than in those with Stage II1A disease ( months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy. John Hoff, Lauren Baldwin, Jason Lefringhouse, Edward Pavlik, Rachel Miller, Christopher DeSimone, Frederick Ueland, Thomas Tucker, Richard Kryscio, and J. R. van Nagell Copyright © 2014 John Hoff et al. All rights reserved. Primary Circulating Prostate Cells Are Not Detected in Men with Low Grade Small Volume Prostate Cancer Tue, 19 Aug 2014 07:13:49 +0000 Objective. To determine if primary circulating prostate cells (CPCs) are found in all men with prostate cancer. Methods and Patients. A prospective study, to analyze all men with an elevated PSA between 4.0 and 10.0 ng/mL undergoing initial biopsy. Primary CPCs were obtained by differential gel centrifugation and detected using standard immunocytochemistry using anti-PSA; positive samples underwent a second process with anti-P504S. A malignant primary CPC was defined as PSA (+) P504S (+) and a test positive if 1 cell/4 mL was detected. Biopsy results were registered as cancer/no-cancer, number of cores positive, and percent infiltration of the cores. Results. 328/1123 (29.2%) of the study population had prostate cancer diagnosed on initial biopsy, and 42/328 (12.8%) were negative for primary CPCs. CPC negative men were significantly older, and had lower PSA levels, lower Gleason scores, and fewer positive cores and with infiltration by the cancer. 38/42 (91%) of CPC negative men complied with the criteria for active surveillance in comparison with 34/286 (12%) of CPC positive men. Conclusions. Using primary CPC detection as a sequential test to select men with an elevated PSA for biopsy, the risk of missing clinically significant prostate cancer is minimal when the patient is primary CPC negative; less than 0.5% of all primary CPC negative men had a clinically significant prostate cancer. Nigel P. Murray, Eduardo Reyes, Cynthia Fuentealba, Nelson Orellana, and Omar Jacob Copyright © 2014 Nigel P. Murray et al. All rights reserved. A Case-Control Study of the Role of Human Papillomavirus in Oesophageal Squamous Cell Carcinoma in Australia Mon, 28 Apr 2014 11:45:58 +0000 Objective. We investigate the prevalence of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) tissues compared to oesophageal tissue from healthy controls, in an Australian cohort. Methods. We conducted a hospital-based case-control study of 99 patients with OSCC and 100 healthy controls to examine the presence of HPV DNA. Paraffin tissues were tested using the PapType high-risk HPV detection and genotyping kit and with INNO-LiPA HPV Genotyping Extra. The biopsy samples were tested for HPV using a PCR-ELISA method based on the L1 consensus primer set PGMY09-PGMY11. Results. HPV DNA of the oncogenic genotype 16 was detected in 1/99 case specimens, a rate of 1010 per 100,000 (95% CI: 30–5500). All control specimens were negative for HPV. Significantly higher rates of smoking, other aerodigestive cancers, and mortality were seen among cases than controls. A pooled analysis of this study and the only other Australian case-control study found that 9/321 cases and 0/155 controls were positive for HPV. The pooled odds ratio for HPV being a risk factor for OSCC was 9.35 (95% CI: 0.47–190.33). Conclusion. Our results suggest that in this multifactorial cancer HPV may be an additional risk factor; although a larger, better powered study is needed. Surabhi S. Liyanage, Eva Segelov, Aisha Malik, Suzanne M. Garland, Sepehr N. Tabrizi, Eleanor Cummins, Holly Seale, Bayzidur Rahman, Aye Moa, Andrew P. Barbour, Philip J. Crowe, and C. Raina MacIntyre Copyright © 2014 Surabhi S. Liyanage et al. All rights reserved. Intensive Care Unit Admission after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Is It Necessary? Tue, 22 Apr 2014 00:00:00 +0000 Introduction. Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a new approach for peritoneal carcinomatosis. However, high rates of complications are associated with CS and HIPEC due to treatment complexity; that is why some patients need stabilization and surveillance for complications in the intensive care unit. Objective. This study analyzed that ICU stay is necessary after HIPEC. Methods. 39 patients with peritoneal carcinomatosis were treated according to strict selection criteria with CS and HIPEC, with closed technique, and the chemotherapy administered were cisplatin 25 mg/m2/L and mitomycin C 3.3 mg/m2/L for 90-minutes at 40.5°C. Results. 26 (67%) of the 39 patients were transferred to the ICU. Major postoperative complications were seen in 14/26 patients (53%). The mean time on surgical procedures was 7.06 hours (range 5−9 hours). The mean blood loss was 939 ml (range 100–3700 ml). The mean time stay in the ICU was 2.7 days. Conclusion. CS with HIPEC for the treatment of PC results in low mortality and high morbidity. Therefore, ICU stay directly following HIPEC should not be standardized, but should preferably be based on the extent or resections performed and individual patient characteristics and risk factors. Late complications were comparable to those reported after large abdominal surgery without HIPEC. Horacio N. López-Basave, Flavia Morales-Vasquez, Carmen Mendez-Herrera, Silvio A. Ñamendys-Silva, Kuauhyama Luna-Ortiz, German Calderillo-Ruiz, Jesús Cabrera Rojas, Erika Ruiz-Garcia, Angel Herrera-Gomez, Juan M. Ruiz-Molina, and Abelardo Meneses Garcia Copyright © 2014 Horacio N. López-Basave et al. All rights reserved. Indicators of Psychiatric Disorders in Different Oncology Specialties: A Prevalence Study Mon, 14 Apr 2014 08:58:55 +0000 Objective. This study evaluated the prevalence of various indicators of psychiatric disorders in Brazilian outpatients with cancer and assessed possible associations with sociodemographic indicators. Materials and Methods. A total of 1,385 patients were evaluated using the following instruments: Patient Health Questionnaire-4 (PHQ-4), Generalized Anxiety Disorder (GAD-7), Fagerström Test for Nicotine Dependence (FTND), and Fast Alcohol Screening Test (FAST). Results. The sample was composed of both genders with a slight predominance of women (55.8%), subjects with incomplete/completed elementary school (59%), married (67.4%), with children (94%), not active from a labor viewpoint (61.6%), and following some type of religion (79.5%). The prevalence of anxiety for the total sample varied between 21.5 and 27.4%. The prevalence of depression was 21.1%, tobacco abuse/dependence was 40.2%, and alcohol was 20.3%. Women had significantly higher levels of anxiety and depression than men. Men had higher levels of substance abuse/dependence indicators than women. Conclusion. These results are consistent with the literature, which attests to the high prevalence of psychiatric disorder indicators in cancer patients, especially compared to the general population. Manuela Polidoro Lima and Flávia L. Osório Copyright © 2014 Manuela Polidoro Lima and Flávia L. Osório. All rights reserved. Androgen Deprivation Therapy and Cardiovascular Risk in Chinese Patients with Nonmetastatic Carcinoma of Prostate Mon, 07 Apr 2014 08:15:05 +0000 Background. Androgen deprivation therapy (ADT) in nonmetastatic prostate cancer is unclear. Recent data suggests possible increase in the cardiovascular risks receiving ADT. The aim of the study was to investigate the cardiovascular outcomes in a cohort of Chinese nonmetastatic prostate cancer patients with no previously documented cardiovascular disease. Methods and Results. 745 patients with no previously documented cardiovascular disease and/or diabetes mellitus diagnosed to have nonmetastatic prostate cancer were recruited. Of these, 517 patients received ADT and the remaining 228 did not. After a mean follow-up of 5.3 years, 60 patients developed primary composite endpoint including (1) coronary artery disease, (2) congestive heart failure, and (3) ischemic stroke. Higher proportion of patients on ADT (51 patients, 9.9%) developed composite endpoint compared with those not on ADT (9 patients, 3.9%) with hazard ratio (HR) of 2.06 (95% confidence interval (CI): 1.03–3.24, ). Furthermore, Cox regression analysis revealed that only the use of ADT (HR: 2.1, 95% CI: 1.03–4.25, ) and hypertension (HR: 2.0, 95% CI: 1.21–3.33, ) were independent predictors for primary composite endpoint. Conclusion. ADT in Chinese patients with nonmetastatic prostate cancer with no previously documented cardiovascular disease was associated with subsequent development of cardiovascular events. Gang Huang, Chun-Yip Yeung, Ka Kui Lee, Jianxiong Liu, Kwan Lun Ho, Ming-Kwong Yiu, Karen Siu-Ling Lam, Hung-Fat Tse, Thomas Yau, and Chung-Wah Siu Copyright © 2014 Gang Huang et al. All rights reserved. Endoscopic Oncology Mon, 31 Mar 2014 13:45:47 +0000 Everson L. A. Artifon, Takao Itoi, Jose G. de la Mora Levy, and Juan J. Vila Copyright © 2014 Everson L. A. Artifon et al. All rights reserved. Pathogenesis and Nomenclature of Odontogenic Carcinomas: Revisited Sun, 30 Mar 2014 09:19:53 +0000 Odontogenic carcinoma is rare group of malignant epithelial odontogenic neoplasms with characteristic clinical behavior and histological features, which requires an aggressive surgical approach. The pathogenesis of this rare group remains still controversial and there have been many varied opinions over the classification of this rare group of lesions. As there have not been many reviews on odontogenic carcinoma, the existing knowledge is mostly derived from the published case reports. This review is discussing the pathogenetic mechanisms and is updating the knowledge on nomenclature system of less explored odontogenic carcinomas. This review might throw light on the pathogenesis and nomenclature system of odontogenic carcinoma and this knowledge may be applied therapeutically. Swagatika Panda, Sujit Ranjan Sahoo, Gunjan Srivastav, Subrat Padhiary, Kanika Singh Dhull, and Sonia Aggarwal Copyright © 2014 Swagatika Panda et al. All rights reserved. The Efficacy of Bisphosphonates in Preventing Aromatase Inhibitor Induced Bone Loss for Postmenopausal Women with Early Breast Cancer: A Systematic Review and Meta-Analysis Wed, 26 Mar 2014 11:28:57 +0000 Objectives. We aim to determine the efficacy of bisphosphonates in preventing aromatase inhibitor induced bone loss (AIBL) in postmenopausal women with early breast cancer. The secondary objective was to determine the safety of bisphosphonates. Materials and Methods. We searched electronic databases in a time period of 1995 January to 2013 June. Random effects meta-analytical models were used; between study heterogeneity and publication bias was assessed. Results. A total of six eligible studies reported the BMD T score of LS at 12 months and from that 3 trials of Zoledronic acid compared the change in BMD in immediate ZOL versus delayed ZOL done with subgroups like patients with normal BMD at baseline (OR = 5.402, 95% CI = 1.329–21.959, value = 0.018) and osteopenic BMD at baseline (OR = 4.008, 95% CI = 2.249–7.143, value = 0.0002). Both had a significant decrease in BMD that favoured the delayed ZOL; 3 trials of risedronate and ibandronate also had a significant decrease in BMD in AIs alone group. Immediate ZOL versus delayed ZOL also showed increased risk of getting an ADR in immediate group. Conclusion. Third generation bisphosphonates has an effect on BMD of patients who are on treatment of AIs in breast cancer. Furthermore, the patients treated with immediate ZOL had a significantly high risk of musculoskeletal ADR’s than patients with delayed ZOL. Pooleriveetil Padikkal Anagha and Suchandra Sen Copyright © 2014 Pooleriveetil Padikkal Anagha and Suchandra Sen. All rights reserved. Disseminated Tumor Cells in Bone Marrow of Gastric Cancer Patients: Correlation with Tumor Hypoxia and Clinical Relevance Tue, 11 Feb 2014 09:20:44 +0000 Aim. The evaluation of the clinical relevance of disseminated tumor cells (DTCs) in bone marrow (BM) of patients with gastric cancer (GC) and their association with primary tumor hypoxia. Patients and Methods. 89 resected specimens were used. DTCs were detected using immunocytochemistry, the level of tumor hypoxia using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1) expression using immunohistochemistry, and MMP-2 and MMP-9 activity using zymography. Results. DTCs were detected in 51.4% of GC patients with M0. There was significant correlation between frequency of DTCs in BM and level of tumor hypoxia (). DTCs presence was accompanied with Flt-1 positivity of BM. The correlation between DTCs and tumor VEGF expression in patients with M0 was shown (). Activity of MMP-2 and MMP-9 in BM was linked with DTCs in patients with M0 (). Overall survival (OS) of patients with M0 and DTCs was shorter than that of patients without DTCs (patients in both groups were operated only) (). Conclusion. Appearance of DTCs correlates with hypoxia level in primary tumors. Detection of DTCs in GC patients may be relevant indicator for adjuvant chemotherapy using. Larissa Bubnovskaya, Antonina Kovelskaya, Lilya Gumenyuk, Irina Ganusevich, Lesya Mamontova, Victor Mikhailenko, Dmitry Osinsky, Sergej Merentsev, and Sergej Osinsky Copyright © 2014 Larissa Bubnovskaya et al. All rights reserved. Nuclear Pattern of CXCR4 Expression Is Associated with a Better Overall Survival in Patients with Gastric Cancer Mon, 10 Feb 2014 13:02:56 +0000 Introduction. Previous studies have shown that stromal-derived factor-1 (CXCL12) and its receptor, CXCR4, play a crucial role in metastasis of various tumors. Similarly, it has been cleared that CXCR4 is expressed on the cell surface of gastric cancers. However, nuclear expression of CXCR4 and its clinical importance have not been yet studied. Materials and Methods. Herein, we studied the expression of CXCR4 in gastric samples from patients with gastric adenocarcinoma as well as human gastric carcinoma cell line, AGS, by employing RT-PCR, immunohistochemistry, and flow cytometry techniques. Results. RT-PCR data showed that CXCR4 is highly expressed on AGS cells. This was confirmed by IHC and FACS as CXCR4 was detected on cell membrane, in cytoplasm, and in nucleus of AGS cells. Moreover, we found that both cytoplasmic and nuclear CXCR4 are strongly expressed in primary gastric cancer and the cytoplasmic pattern of CXCR4 tends to be associated with a shorter overall survival than nuclear staining. In conclusion, we present evidence for the first time that both cytoplasmic and nuclear expression of CXCR4 are detectable in gastric cancer tissues. However, the role of both cytoplasmic and nuclear CXCR4 needs to be further elucidated. Bahram Nikkhoo, Ali Jalili, Shohreh Fakhari, Farshad Sheikhesmaili, Fardin Fathi, Daem Rooshani, Mohammad Ali Hoseinpour Feizi, and Mehrnoush Nikzaban Copyright © 2014 Bahram Nikkhoo et al. All rights reserved. Predictors of Venous Thromboembolic Events Associated with Central Venous Port Insertion in Cancer Patients Sun, 09 Feb 2014 08:49:29 +0000 Insertion of central venous port (CVP) catheter in the cancer population is associated with increased incidence of venous thromboembolic events (VTE). However, trials have shown limited benefit of antithrombotic treatment to prevent catheter-related venous thrombosis. This prospective observational cohort study was designed to assess the incidence of VTE closely related to CVP implantation in patients with cancer and undergoing chemotherapy, and to identify a high risk subgroup of patients. Between February 2006 and December 2011, 1097 consecutive cancer patients with first CVP implantation were included. Catheter-related VTE were defined as deep venous thrombosis in the arm, with or without pulmonary embolism (PE), or isolated PE. The incidence of CVP-associated VTE was 5.9% (IC95 4.4–7.3%) at 3 months, and 11.3% (IC95 9.4–13.2%) at 12 months. The incidence of any VTE was 7.6% (IC95 6.0–9.3%) at 3 months, and 15.3% (IC95 13.1–17.6%) at 12 months. High Khorana risk score and lung cancer were significant predictors of 3 month VTE. In conclusion, this large cohort study of patients with first CVP catheter implantation confirms the high incidence of VTE associated with the CVP implantation and allow identifying high risk patients who may benefit from thromboprophylaxis. Christine Hohl Moinat, Daniel Périard, Adrienne Grueber, Daniel Hayoz, Jean-Luc Magnin, Pascal André, Marc Kung, and Daniel C. Betticher Copyright © 2014 Christine Hohl Moinat et al. All rights reserved. Prognostic Role of 14F7 Mab Immunoreactivity against N-Glycolyl GM3 Ganglioside in Colon Cancer Thu, 30 Jan 2014 12:03:00 +0000 Purpose. To assess the prognostic role of 14F7 Mab immunoreactivity, against N-Glycolyl GM3 ganglioside, in patients with colon cancer (CC) and to evaluate the relationship between its expression and clinicopathological features. Methods. Paraffin-embedded specimens were retrospectively collected from 50 patients with CC operated between 2004 and 2008. 14F7 Mab staining was determined by immunohistochemistry technique and its relation with survival and clinicopathologic features was evaluated. Results. The reactivity of 14F7 Mab was detected in all cases. Most cases had high level of immunostaining (70%) that showed statistical correlation with TNM stage . In univariate survival analysis, level of 14F7 Mab immunoreactivity , TNM Stage and lymphovascular invasion were significant prognostic factors for overall survival. Among these variables, level of 14F7 Mab immunoreactivity and TNM stage were independent prognostic factors on multivariate analysis. Conclusions. This study is the first approach on the prognostic significance of 14F7 Mab immunoreactivity in patients with colon adenocarcinoma and this assessment might be used in the prognostic estimate of CC, although further studies will be required to validate these findings. Tania Lahera, Adanays Calvo, Griselda Torres, Charles E. Rengifo, Santiago Quintero, María del Carmen Arango, Debora Danta, José M. Vázquez, Xiomara Escobar, and Adriana Carr Copyright © 2014 Tania Lahera et al. All rights reserved. Evaluation of p53, HoxD10, and E-Cadherin Status in Breast Cancer and Correlation with Histological Grade and Other Prognostic Factors Thu, 30 Jan 2014 10:05:52 +0000 Background. Study of tumor molecular characteristics is necessary to understand both the risk of breast cancer recurrence and the response to therapy. Aims. To evaluate p53, HoxD10, and E-cadherin status in breast cancer and to correlate with histological grade and other prognostic factors. Material and Methods. The study was conducted in 60 cases of invasive ductal carcinoma NOS with 20 cases belonging to each grade and evaluation of p53 was done by IHC and that of HoxD10 and E Cadherin status by PCR and correlation was done with histological grade and other prognostic factors. Result. p53 expression was seen in 71.67% (43/60) of the tumors. HoxD10 gene was downregulated in 46.67% (28/60) of the tumors. p53 overexpression and lower HoxD10 mRNA levels showed statistically significant association higher histological grade of the tumor (). CDH1 gene mutation was seen in 60% (15/25) of the tumors. No significant association was found between p53 expression, HoxD10 gene, CDH1 gene mutation, and other prognostic factors. Conclusion. p53 over expression and lower HoxD10 mRNA levels were found to be significantly associated with higher grade tumours. This suggests that p53 and HoxD10 gene play an important tumor suppressor role and the loss of which results in breast cancer progression. Preethi Sekar, Jyotsna Naresh Bharti, Jitendra Singh Nigam, Ankit Sharma, and Priyanka Bhatia Soni Copyright © 2014 Preethi Sekar et al. All rights reserved. Ethanolic Neem (Azadirachta indica) Leaf Extract Prevents Growth of MCF-7 and HeLa Cells and Potentiates the Therapeutic Index of Cisplatin Thu, 30 Jan 2014 08:09:28 +0000 The present study was designed to gain insight into the antiproliferative activity of ethanolic neem leaves extract (ENLE) alone or in combination with cisplatin by cell viability assay on human breast (MCF-7) and cervical (HeLa) cancer cells. Nuclear morphological examination and cell cycle analysis were performed to determine the mode of cell death. Further, to identify its molecular targets, the expression of genes involved in apoptosis, cell cycle progression, and drug metabolism was analyzed by RT-PCR. Treatment of MCF-7, HeLa, and normal cells with ENLE differentially suppressed the growth of cancer cells in a dose- and time-dependent manner through apoptosis. Additionally, lower dose combinations of ENLE with cisplatin resulted in synergistic growth inhibition of these cells compared to the individual drugs (combination index <1). ENLE significantly modulated the expression of bax, cyclin D1, and cytochrome P450 monooxygenases (CYP 1A1 and CYP 1A2) in a time-dependent manner in these cells. Conclusively, these results emphasize the chemopreventive ability of neem alone or in combination with chemotherapeutic treatment to reduce the cytotoxic effects on normal cells, while potentiating their efficacy at lower doses. Thus, neem may be a prospective therapeutic agent to combat gynecological cancers. Chhavi Sharma, Andrea J. Vas, Payal Goala, Taher M. Gheewala, Tahir A. Rizvi, and Arif Hussain Copyright © 2014 Chhavi Sharma et al. All rights reserved. Incidence of Mast Cells in Oral Squamous Cell Carcinoma: A Short Study Thu, 23 Jan 2014 00:00:00 +0000 Mast cells are regarded as complex and multifunctional cells, playing a significant role in immunopathology and a substantial role in tumor angiogenesis. Angiogenesis is a complex process that is tightly regulated by various growth factors in which mast cells act directly by releasing angiogenic factors and henceforth promoting tumor growth and metastasis. The aim of this study is to evaluate the number of mast cells in tissue sections of oral squamous cell carcinoma (OSCC) in comparison with normal mucosa. A total of 40 cases (20 OSCC and 20 normal mucosa) were stained with 1% toluidine blue and the quantitative analysis was done by using light microscope under 400x magnification. A significant increase in the mast cell count was observed in the sections of OSCC when compared to normal mucosa suggesting their contributing role in tumor growth and progression. A. Anuradha, B. Kiran Kumar Naik, G. Vijay Srinivas, Ramisetty Sabitha Devi, and H. K. Puneet Copyright © 2014 A. Anuradha et al. All rights reserved. AR-A 014418 Used against GSK3beta Downregulates Expression of hnRNPA1 and SF2/ASF Splicing Factors Thu, 02 Jan 2014 13:02:49 +0000 Glioblastoma is one of the most aggressive forms of primary brain tumors of glial cells, including aberrant regulation of glycogen synthase kinase 3β (GSK3β) and splicing factors deregulation. Here, we investigate the role of small molecule AR-A014418 and Manzamine A against GSK3 kinase with factual control on splicing regulators. AR-A 014418, 48 hrs posttreatment, caused dose (25–100 μM) dependent inhibition in U373 and U87 cell viability with also inhibition in activating tyrosine phosphorylation of GSK3alpha (Tyr 279) and beta (Tyr 216). Furthermore, inhibition of GSK3 kinase resulted in significant downregulation of splicing factors (SRSF1, SRSF5, PTPB1, and hnRNP) in U87 cells with downregulation of antiapoptotic genes such as BCL2, BCL-xL, Survivin, MCL1, and BMI1. Similarly, downregulation of splicing factors was also observed in U373 glioma cell after using SiRNA against AKT and GSK3beta kinase. In addition, potential roles of AR-A014418 in downregulation of splicing factors were reflected with decrease in Anxa7 (VA) variant and increase in Anxa7 WT tumor suppressor transcript and protein. The above results suggest that inhibition of GSK3beta kinase activation could be the beneficial strategy to inhibit the occurrence of alternative cancer escape pathway via downregulating the expression of splicing regulators as well as apoptosis. Ajay K. Yadav, Vidhi Vashishta, Nidhi Joshi, and Pankaj Taneja Copyright © 2014 Ajay K. Yadav et al. All rights reserved. Detection of TP53 R249 Mutation in Iranian Patients with Pancreatic Cancer Mon, 30 Dec 2013 13:10:58 +0000 The TP53 gene encodes tumor protein p53 which play a major role in the etiology of pancreatic cancer. The important role of codon 249 of TP53 for binding of p53 to its sequence-specific consensus site in DNA has been revealed by crystallography’s studies, and mutation at this codon was detected in the plasma of some human cancers. The TP53 Mut assessor software within the International Agency for Research on Cancer (IARC) TP53 Database was performed to evaluate every possible mutation at codon 249. DNA was extracted from the plasma of 133 pancreatic cancer patients and 85 noncancer-bearing individuals. Exon 7 in TP53 was amplified, and mutation at R249 was identified by the endonuclease cleavage of HaeIII. The group of patients showed a frequency of 11% (22 of 133 samples) R249 mutation compared to 3.5% (3 of 85 samples) in the group of control which was significant (). This mutation demonstrated statistically significant association with pancreatic cancer risk in unadjusted odds ratio (OR: 3.74, 95% CI: 1.1–13.2; ); however when adjusted for confounding factors, it was marginally significant because of lower control samples. These findings demonstrate that mutation at R249 of TP53 can be considered for increasing risk of pancreatic cancer that needs more research. Ashraf Mohamadkhani, Elnaz Naderi, Maryam Sharafkhah, Hamid Reza Fazli, Malihe Moradzadeh, and Akram Pourshams Copyright © 2013 Ashraf Mohamadkhani et al. All rights reserved. Serum p53 Antibody Is Not Associated with p53 Immunoreactivity in Patients with Pancreatobiliary Cancers Wed, 18 Dec 2013 15:48:14 +0000 Background. Recent diagnostic imaging tests contribute to improving the diagnosis of pancreatobiliary cancers. However, it is not practical to perform these tests for all patients as screening. Thus, less-invasive and simple screening tests are still required. A method to detect the IgG antibody induced in serum against the p53 protein accumulating due to p53 gene mutation, as a biomarker, was developed around 1990. Method. 35 patients with pancreatic cancer, 12 patients with biliary tract cancer, and 31 patients with benign pancreatobiliary diseases were entered into this study. Measurement of serum anti-p53 antibody was conducted in all patients. In addition, the rate of p53 protein overexpression was examined in those cases that could be examined pathologically. Result. Among all patients in the pancreatic cancer and biliary tract cancer groups, there was no patient with serum anti-p53 antibody positive value that exceeded the standard value. The rate of p53 protein overexpression was 48.0% in the patients with pancreatobiliary cancers and 0% in the benign pancreatobiliary diseases group. Conclusion. Serum anti-p53 antibody measurement does not contribute to the diagnosis of pancreatobiliary cancers. Instead, traditional p53 immunostaining still appears to be valuable in combination with standard procedures. Junko Umeda, Takao Itoi, Atsushi Sofuni, Fumihide Itokawa, Toshio Kurihara, Takayoshi Tsuchiya, Kentaro Ishii, Shujiro Tsuji, Nobuhito Ikeuchi, Reina Tanaka, Ryosuke Tonozuka, Mitsuyoshi Honjo, Shuntaro Mukai, Toshitaka Nagao, Hisashi Oshiro, and Fuminori Moriyasu Copyright © 2013 Junko Umeda et al. All rights reserved. Antiproliferative and Apoptotic Effects of a Specific Antiprostate Stem Cell Single Chain Antibody on Human Prostate Cancer Cells Tue, 10 Dec 2013 17:48:09 +0000 Prostate stem cell antigen (PSCA) is a highly glycosylated cell surface protein which is overexpressed in several malignancies including prostate, pancreas, and urinary bladder cancers. Tumor suppression has been reported by anti-PSCA antibody. Small and high affinity single chain antibodies (scFv) have been introduced as effective agents for cancer immunotargeting approaches. In the present study, we used a phage antibody display library of scFv and selected two antibodies against two immunodominant epitopes of PSCA by panning process. The reactivity of the scFvs for the corresponding epitopes was determined by phage ELISA. The binding specificity of antibodies to PSCA-expressing prostate cancer cell line, DU-145, was analyzed by flow cytometry. The antiproliferative and apoptotic induction effects were evaluated by MTT and Annexin-V assays, respectively. Results represented functional scFv C5-II which could bind specifically to DU-145 cells and significantly inhibited the proliferation of these cells (61%) with no effect on PSCA-negative cells. The antibody also induced apoptosis in the PSCA expressing cells. The percentage of the apoptotic cells after 24 hrs of exposure to 500 scFv/cell was 33.80%. These results demonstrate that the functional anti-PSCA scFv C5-II has the potential to be considered as a new agent for targeted therapy of prostate cancer. Foroogh Nejatollahi, Soghra Abdi, and Mahdi Asgharpour Copyright © 2013 Foroogh Nejatollahi et al. All rights reserved. Gastroduodenal Outlet Obstruction and Palliative Self-Expandable Metal Stenting: A Dual-Centre Experience Sun, 10 Nov 2013 10:59:03 +0000 Background. Self-expandable metal stents (SEMs) are increasingly being utilised instead of invasive surgery for the palliation of patients with malignant gastroduodenal outlet obstruction. Aim. To review two tertiary centres’ experience with placement of SEMs and clinical outcomes. Methods. Retrospective analysis of prospectively collected data over 12 years. Results. Ninety-four patients (mean age, 68; range 28–93 years) underwent enteral stenting during this period. The primary tumour was gastric adenocarcinoma in 27 (29%) patients, pancreatic adenocarcinoma in 45 (48%), primary duodenal adenocarcinoma in 8 (9%), and cholangiocarcinoma and other metastatic cancers in 14 (16%). A stent was successfully deployed in 95% of cases. There was an improvement in gastric outlet obstruction score (GOOS) in 84 (90%) of patients with the ability to tolerate an enteral diet. Median survival was 4.25 months (range 0–49) without any significant differences between types of primary malignancy. Mean hospital stay was 3 days (range 1–20). Reintervention rate for stent related complications was 5%. Conclusion. The successful deployment of enteral stents achieves excellent palliation often resulting in the prompt reintroduction of enteral diet and early hospital discharge with minimal complications and reintervention. Nik S. Ding, Sina Alexander, Michael P. Swan, Christopher Hair, Patrick Wilson, Emma Clarebrough, and David Devonshire Copyright © 2013 Nik S. Ding et al. All rights reserved. Efficacy of Goshajinkigan for Oxaliplatin-Induced Peripheral Neuropathy in Colorectal Cancer Patients Thu, 07 Nov 2013 09:34:18 +0000 Objective. To evaluate the efficacy of Goshajinkigan for oxaliplatin-induced peripheral neuropathy in colorectal cancer patients. Patients. Colorectal cancer patients () who received ≥4 weeks of Goshajinkigan for oxaliplatin-induced peripheral neuropathy during chemotherapy at Kyoto Prefectural University of Medicine were (Goshajinkigan group) compared to 44 patients who had not received Goshajinkigan during the same period (non-Goshajinkigan group). Main Outcome Measures. The effect of Goshajinkigan was graded as curative, effective, stabilizing, or deleterious. The relationships between the grade of peripheral neuropathy and the dose of oxaliplatin in the Goshajinkigan and non-Goshajinkigan groups were evaluated. Results. The effect of Goshajinkigan on peripheral neuropathy in the Goshajinkigan group was curative, effective, stabilizing, and deleterious in 3.4, 20.7, 69.0, and 6.9% of patients, compared to the effect in the non-Goshajinkigan group (4.5, 15.9, 45.5, and 34.1%). The ratio of deleterious effects was significantly different between these two groups (). A Kaplan-Meier analysis in relation to the cumulative dose of oxaliplatin showed that the incidence of grade 3 peripheral neuropathy tended to be less in the Goshajinkigan group (). There were no significant differences in time to treatment failure and severe adverse events between these two groups. Conclusions. Goshajinkigan prevented exacerbation of oxaliplatin-induced peripheral neuropathy. This trial is registered with UMIN000009956 Naohisa Yoshida, Toyoshi Hosokawa, Takeshi Ishikawa, Nobuaki Yagi, Satoshi Kokura, Yuji Naito, Masayoshi Nakanishi, Yukihito Kokuba, Eigo Otsuji, Haruo Kuroboshi, Masafumi Taniwaki, Tetsuya Taguchi, Hajime Hosoi, Terukazu Nakamura, and Tsuneharu Miki Copyright © 2013 Naohisa Yoshida et al. All rights reserved. Proteomics of Uveal Melanoma: A Minireview Tue, 03 Sep 2013 08:34:37 +0000 Uveal melanoma (UM) continues to be associated with a high mortality rate of up to 50% due to metastatic spread primarily to the liver. Currently there are relatively effective treatments for the primary tumor, though the management of the metastatic disease remains inadequate. Conventional diagnostic tools have a low sensitivity for detecting metastasis, and early detection of metastatic spread would allow more treatment options that could ultimately increase survival of UM patients. Advanced proteomic methods have already helped to find potential biomarkers associated with UM pathogenesis and metastasis. In the present review we discuss the field of proteomics in relation to studies elucidating biomarkers of UM, where proteins such as S-100β, osteopontin (OPN), and melanoma inhibitory activity (MIA) have been shown to be associated with metastasis. Søren K. O. Abildgaard and Henrik Vorum Copyright © 2013 Søren K. O. Abildgaard and Henrik Vorum. All rights reserved. Endoscopic Submucosal Dissection for Large Colorectal Tumor in a Japanese General Hospital Thu, 29 Aug 2013 14:32:20 +0000 Background and Aims. Endoscopic submucosal dissection (ESD) is not widely used in large colorectal lesions because of technical difficulty and possible complications. We aimed to examine the efficacy and safety of ESD for large colorectal neoplasms. Patients and Methods. During the past 5 years, 608 cases of colorectal neoplasm (≧20 mm) were treated by ESD. They were divided into Group A (20–49 mm, 511 cases) and Group B (≧50 mm, 97 cases). Results. The average age, lesion size, and procedure time were 67.4 years, 30.0 mm, and 60.0 min in Group A, and they were 67.1 years, 64.2 mm, and 119.6 min in Group B. En bloc resection rates were 99.2% and 99.0% (), and complication rates were 4.1% and 9.9% (). Complications in Group A consisted of perforation (2.7%), bleeding (1.2%), and ischemic colitis (0.2%). Those in Group B were perforation (8.2%) and bleeding (1.0%). Two cases in Group A and none in Group B required emergency surgery for perforation. Conclusions. There was no difference in efficacy between Groups A and B. Complications were more frequent in Group B, but all perforations in Group B were successfully managed conservatively. ESD can be effective and safe for large colorectal tumors. Ken Ohata, Kouichi Nonaka, Yohei Minato, Yoshitsugu Misumi, Tomoaki Tashima, Meiko Shozushima, Takahiro Mitsui, and Nobuyuki Matsuhashi Copyright © 2013 Ken Ohata et al. All rights reserved. Neoadjuvant Chemotherapy and Targeted Therapy in Breast Cancer: Past, Present, and Future Tue, 20 Aug 2013 10:15:50 +0000 Traditionally, neoadjuvant treatment for breast cancer was preserved for locally advanced and inflammatory disease, converting an inoperable to a surgical resectable cancer. In recent years, neoadjuvant therapy has become an accepted treatment option also for lower tumor stages in order to increase the rate of breast conserving therapy and to reduce the extent of surgery. Furthermore, treatment response can be monitored, and therefore, patient compliance may be increased. Neoadjuvant trials, additionally, offer the opportunity to evaluate new treatment options in a faster way and with fewer patients than large adjuvant trials. Compared to the metastatic setting, the issue of acquired resistance and pretreatments, which may distort treatment efficacy, can be avoided. New trial designs like window-of-opportunity trials or postneoadjuvant trials provide the chance to identify tumor sensitivity or to overcome tumor resistance in early tumor stages. In particular, in HER2-positive breast cancer, the neoadjuvant approach yielded great successes. The dual HER2 blockade with trastuzumab and pertuzumab recently showed the highest pCR rates ever reported. Many new drugs are in clinical testing with the aim to further increase pCR rates. Whether this endpoint really represents a surrogate for long-term outcome is not answered yet and will be discussed in this review. Simon P. Gampenrieder, Gabriel Rinnerthaler, and Richard Greil Copyright © 2013 Simon P. Gampenrieder et al. All rights reserved.