Journal of Cancer Research The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Factors Affecting the Practices of Cervical Cancer Screening among Female Nurses at Public Health Institutions in Mekelle Town, Northern Ethiopia, 2014: A Cross-Sectional Study Mon, 29 Feb 2016 12:24:54 +0000 Objective. In Ethiopia, the age-adjusted incidence rate of cervical cancer is high, 35.9 per 100,000 women. Despite this fact, cervical cancer screening coverage in Ethiopia is very low. The objective of this study is to assess the magnitude and factors affecting the practices of cervical cancer screening among female nurse in Mekelle Town, Tigray, Northern Ethiopia, 2014. Methods. This study used a cross-sectional design. Bivariate and multivariate logistic regression was used to evaluate factors associated with cervical cancer screening practice. Results. A total of 225 female nurses participated in the study. The magnitude of cervical cancer screening practice among these nurses was 10.7%, within the past five years of the survey. Attitude and work place of the respondents were significantly associated with a history of cervical cancer screening practices with an adjusted odds ratio (AOR) of 3.023, 95% CI (1.134–8.059), and 3.424, 95% CI (1.080–10.853), respectively. Conclusion. The study showed that the magnitude of the cervical screening practice is very low among nurse health professionals. Negative attitude and workplace were identified to be the predictors of decision for cervical cancer test. Mihret Gebreegziabher, Nigus Gebremedhin Asefa, and Semarya Berhe Copyright © 2016 Mihret Gebreegziabher et al. All rights reserved. Molecular Docking Study Characterization of Rare Flavonoids at the Nac-Binding Site of the First Bromodomain of BRD4 (BRD4 BD1) Sun, 22 Mar 2015 13:39:29 +0000 ε-N-Acetylation of lysine residues (Kac) is one of the most frequently occurring posttranslational modifications (PTMs) which control gene transcription and a vast array of diverse cellular functions. Bromodomains are epigenetic regulators involved in posttranslational modification. In silico docking studies were carried out to evaluate the binding potential of selected rare flavonoids on to Nac binding site of BD1 domain of BRD4 BET family proteins. Rare flavonoids like 3-O-acetylpinobanksin, naringenin triacetate, and kaempferol tetraacetate were found to occupy the WPF shelf and at the same time they exhibited a better binding affinity with multiple crystal structures of first bromodomain BRD4 (BRD4 BD1) when compared with the known inhibitors. Karthik Dhananjayan Copyright © 2015 Karthik Dhananjayan. All rights reserved. CXCR4 Expression in Gastric Cancer and Bone Marrow: Association with Hypoxia-Regulated Indices, Disseminated Tumor Cells, and Patients Survival Wed, 25 Feb 2015 14:46:52 +0000 Aim. The analysis of the association of CXCR4 expression in gastric cancer (GC) and bone marrow (BM) with clinical characteristics. Patients and Methods. 65 patients with GC were investigated. Immunohistochemistry, immunocytochemistry, NMR-spectroscopy, and zymography were used. Results. CXCR4 was expressed in 78.5% of GC specimens and correlated with tumor hypoxia (), VEGF expression (), and gelatinases activity (). CXCR4-positive cells in GC were detected in 80% of patients with disseminated tumor cells (DTCs). Overall survival (OS) of patients with CXCR4-positive tumors was poorer than that of patients with CXCR4-negative tumors (). The CXCR4-positive cells in BM were found in 46% of all patients and in 56% of patients with DTCs. CXCR4 expression in BM was not associated with OS. Risk of unfavourable outcome is increased in patients with CXCR4-positive tumors (). CXCR4 expression in BM was positively associated with DTCs, especially in patients with M0 category. Risk of unfavourable outcome is increased in patients with category and with both CXCR4-positive BM and DTCs (). Conclusions. CXCR4 expression in tumor was positively correlated with hypoxia level and VEGF expression in tumor as well as OS. CXCR4 expression in BM is associated with DTCs. Dmitry Osinsky, Antonina Kovelskaya, Larissa Bubnovskaya, Irina Ganusevich, Lilya Gumenyuk, Sergej Merentsev, Sergej Osinsky, and Lesya Mamontova Copyright © 2015 Dmitry Osinsky et al. All rights reserved. Validation of Microcirculatory Parameters Derived from the Standard Two-Compartment Model with Murine Xenografts Model Mon, 16 Feb 2015 10:56:12 +0000 The purpose of this study was to validate DCE-MRI parameters such as blood flow (), permeability surface area product (PS), fractional intravascular space (), and fractional extracellular extravascular space (), obtained using a standard two-compartment model against other established analysis methods and histological indices. DCE-MRI datasets of 28 mice implanted with various human cancer xenografts were acquired and analyzed. Statistically significant correlations were found between the parameters derived from the standard two-compartment model (, , , and PS) with the histological markers of intravascular and interstitial space and with the corresponding flow and permeability estimates obtained by the initial slope method and Patlak plot, respectively. Septian Hartono, Choon Hua Thng, Richard Weijie Ong, Quan Sing Ng, Tony Kiat Hon Lim, Sidney Wing Kwong Yu, The Hung Huynh, Laurent Martarello, and Tong San Koh Copyright © 2015 Septian Hartono et al. All rights reserved. Hepatocellular Carcinoma Is the Most Frequent Final Diagnosis of Focal Liver Lesions Identified in a Cross-Sectional Evaluation of Patients with Chronic Liver Disease in Saudi Arabia Tue, 06 Jan 2015 09:08:15 +0000 Background. Hepatocellular carcinoma (HCC) is a frequent diagnosis in patients with chronic liver disease (CLD) and a newly identified liver lesion, although benign diseases may also be responsible for this finding. Objective. To evaluate the characteristics of focal liver lesions in a population of patients with CLD not under surveillance for HCC in the Middle East. Methods. We performed a cross-sectional study evaluating 77 patients with CLD and a focal liver lesion identified during ultrasonography. Patients’ characteristics were analyzed on the basis of the final diagnosis (HCC versus benign lesions). Results. The most frequent diagnosis was HCC (64.9%). These patients were older (median age 64 versus 55 years, ) and cirrhotics (80.0% versus 51.9%, ), with multinodular lesions (58.0% versus 29.6%, ) and portal vein thrombosis (24.0% versus 0%, ) compared to patients with benign lesions. Prevalence of elevated alpha-fetoprotein (>10 ng/mL) was similar in both groups (80.0% versus 88.9%, ). Cirrhosis (odds ratio: 3.283) and multinodularity (odds ratio: 2.898) were independently associated with HCC. Conclusions. HCC is the most common diagnosis in Middle-Eastern patients with CLD and a liver lesion identified outside HCC surveillance programs, especially in cirrhotic patients. In these patients, elevated alpha-fetoprotein does not differentiate HCC from benign lesions. Adnan Agha, Manuele Furnari, Rafaat Morched Chakik, Mamdouh M. Abdulhadi Ali, Dib Alsaudi, Mohammed Bazeed, Vincenzo Savarino, and Edoardo G. Giannini Copyright © 2015 Adnan Agha et al. All rights reserved. AgCu Bimetallic Nanoparticles under Effect of Low Intensity Ultrasound: The Cell Viability Study In Vitro Tue, 30 Dec 2014 11:14:20 +0000 The effects of metallic nanoparticles as cytotoxicity or antibacterial activity are widely known. It is also obvious that ultrasound is one of the most widely used therapeutic modalities in medicine. The effect of application of therapeutical ultrasonic field in the presence of metallic nanoparticles AgCu <100 nm modified by phenanthroline or polyvinyl alcohol was examined on human ovarian carcinoma cells A2780. Metallic nanoparticles were characterized by electron microscopy and by measuring of zeta potential. The cell viability was tested by MTT test. The experimental results indicate a significant decrease of cell viability, which was affected by a combined action of ultrasound field and AgCu nanoparticles. The maximum decrease of cells viability was observed for nanoparticles modified by phenanthroline. The effect of metallic nanoparticles on human cell in presence of ultrasound exposure was found—a potential health risk or medical advantage of targeted therapy in the future. Vladan Bernard, Ondřej Zobač, Jiří Sopoušek, and Vojtěch Mornstein Copyright © 2014 Vladan Bernard et al. All rights reserved. Association between Latitude and Breast Cancer Incidence in Mainland Australian Women Tue, 09 Dec 2014 06:45:37 +0000 Aim. To investigate whether breast cancer incidence increases with increasing latitude in mainland Australian women. Methods. A cross-sectional study of female breast cancer and cutaneous melanoma incidence 2002–2006 by 5-year age group and local government area. Latitude, Accessibility/Remoteness Index of Australia (ARIA), and Index of Relative Socioeconomic Disadvantage (IRSD) were assigned to local government areas. Latitude was grouped into bands (≤27°S; >27–30°S; >30–33°S; >33–36°S, and >36°S), and IRSD was divided into quintiles and ARIA into four categories. Breast cancer rates were age standardized using the direct method. The joint effects of latitude, age, IRSD, and ARIA on incidence of breast cancer and cutaneous melanoma were assessed using multiple logistic regressions. Results. At latitudes south of 30°S, rates of breast cancer were over double that north of 27°S (76.4 versus 160.2–176.5). Age-adjusted odds ratios of breast cancer were increased in all latitudes south of 30°S compared with north of 27°S within each IRSD and ARIA category (all ). After adjusting for age, IRSD, and ARIA, the odds ratio of breast cancer south of 30°S was 1.92 (95% CI 1.84–2.09; ), whereas cutaneous melanoma was 0.65 (95% CI 0.61–0.68; ) times north of 30°S. Discussion. Increasing latitude is positively associated with breast cancer and negatively associated with cutaneous melanoma incidence. These findings support suggestions that increased risk of breast cancer might be explained by lower ultraviolet radiation-induced vitamin D synthesis. Kellie Bilinski, Karen Byth, and John Boyages Copyright © 2014 Kellie Bilinski et al. All rights reserved. Impact of Immunochemotherapy-Related Hepatic Toxicity on the Outcome of HCV-Positive Diffuse Large B-Cell Lymphoma Patients Sun, 30 Nov 2014 11:36:19 +0000 We conducted this prospective study which included 28 de novo CD20-positive DLBCL patients to assess the clinical outcome, treatment response, and hepatic toxicity in DLBCL patients who received rituximab-CHOP as a first line treatment in relation to HCV infection status. We included 7 patients with positive HCV infection (group A) and 21 patients with negative HCV infection (group B). HCV infection was not a significant risk factor for prognosis (1-year event-free survival rates, 71.4% versus 81%, ; overall survival rates, 85.7% versus 90.5%, , for groups A and B, resp.). CR rate was 71.4% (5/7) in group A and 76.2% (16/21) in group B (). Of the 7 patients who were HCV positive, 2 (28.6%) had enzyme flare (grade 2), compared with 1 of the 21 (4.8%) patients who were HCV negative (). Two (28.6%) of the 7 positive HCV infection patients had viral reactivation (1 log10 IU/mL increase in the viral load). No patient required discontinuation of immunochemotherapy owing to hepatotoxicity in either group. In conclusion, HCV infection might not influence the clinical course in DLBCL patients who receive rituximab-CHOP. Close monitoring of hepatic function and viral load is recommended. Fouad Abu-Taleb, Rasha Haggag, Yasser Elnaggar, and Ahmed Embaby Copyright © 2014 Fouad Abu-Taleb et al. All rights reserved. BAY 61-3606, CDKi, and Sodium Butyrate Treatments Modulate p53 Protein Level and Its Site-Specific Phosphorylation in Human Vestibular Schwannomas In Vitro Mon, 20 Oct 2014 00:00:00 +0000 This study is done to evaluate the effect of spleen tyrosine kinase inhibitor (BAY 61-3606), cyclin-dependent kinase inhibitor (CDKi), and sodium butyrate (Na-Bu) on the level and phosphorylation of p53 protein and its binding to murine double minute 2 (MDM2) homologue in human vestibular schwannomas (VS). Primary cultures of the tumor tissues were treated individually with optimum concentrations of these small molecules in vitro. The results indicate modulation of p53 protein status and its binding ability to MDM2 in treated samples as compared to the untreated control. The three individual treatments reduced the level of total p53 protein. These treatments also decreased Ser392 and Ser15 phosphorylated p53 in tumor samples of young patients and Ser315 phosphorylated p53 in old patients. Basal level of Thr55 phosphorylated p53 protein was present in all VS samples and it remained unchanged after treatments. The p53 protein from untreated VS samples showed reduced affinity to MDM2 binding in vitro and it increased significantly after treatments. The MDM2/p53 ratio increased approximately 3-fold in the treated VS tumor samples as compared to the control. The differential p53 protein phosphorylation status perhaps could play an important role in VS tumor cell death due to these treatments that we reported previously. Rohan Mitra, Rohini Keshava, Mathivanan Jothi, Vikas Vazhayil, Indira Devi Bhagavatula, and Rajalakshmi Gope Copyright © 2014 Rohan Mitra et al. All rights reserved. miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model Tue, 14 Oct 2014 09:49:42 +0000 Epithelial to mesenchymal transition is an essential step in advanced cancer development. Many master transcription factors shift their expression to drive this process, while noncoding RNAs families like miR-200 are found to restrict it. In this study we investigated how the tumor suppressor miR-204 and several transcription factors modulate main markers of mesenchymal transformation like E- and N-cadherin, SLUG, VEGF, and SOX-9 in prostate cancer cell line model (LNCaP, PC3, VCaP, and NCI-H660). We found that SLUG, E-cadherin, and N-cadherin are differentially modulated by miR-204, using miR-204 specific mimics and inhibitors and siRNA gene silencing (RUNX2, ETS-1, and cMYB). The genome perturbation associated TMPRSS2-ERG fusion coincided with shift from tumor-suppressor to tumor-promoting activity of this miRNA. The ability of miR-204 to suppress cancer cell viability and migration was lost in the fusion harboring cell lines. We found differential E-cadherin splicing corroborating to miR-204 modulatory effects. RUNX2, ETS1, and cMYB are involved in the regulation of E-cadherin, N-cadherin, and VEGFA expression. RUNX2 knockdown results in SOX9 downregulation, while ETS1 and cMYB silencing result in SOX9 upregulation in VCaP cells. Their expression was found to be also methylation dependent. Our study provides means for understanding cancer heterogeneity in regard to adapted therapeutic approaches development. Krassimira Todorova, Diana Zasheva, Kristiyan Kanev, and Soren Hayrabedyan Copyright © 2014 Krassimira Todorova et al. All rights reserved. Fibre Diffraction Analysis of Skin Offers a Very Early and Extremely Accurate Diagnostic Test for Prostate Cancer Wed, 17 Sep 2014 08:51:42 +0000 Double blind analysis of a batch of thirty skin tissue samples from potential prostate cancer sufferers correctly identified all “control” patients, patients with high and low grade prostate cancers, the presence of benign prostate hyperplasia (BPH), perineural invasions, and the one lymphatic invasion. Identification was by analysis of fibre diffraction patterns interpreted using a schema developed from observations in nine previous studies. The method, schema, and specific experiment results are reported in this paper, with some implications then drawn. Veronica J. James and Judith M. O’Malley Ford Copyright © 2014 Veronica J. James and Judith M. O’Malley Ford. All rights reserved. The Present Status of the Management of Colon and Rectal Cancer in Nigeria Thu, 21 Aug 2014 00:00:00 +0000 Aim. To demonstrate the possibility of the uniqueness of colorectal cancer (CRC) in the native Nigerian by looking at the different facets of the challenges that management of this disease presents in a tertiary-care hospital in Ibadan, Nigeria. Method. A cohort study starting in 2009 where patients were seen in the out-patient’s clinic. All patients who presented with features suggestive of colon or rectal cancer were studied. Biopsies were performed to confirm CRC (especially rectal cancer); patients were then booked for admission and subsequent operation. Patients were excluded if the histopathology of a resected or biopsied mass turned out to be noncancerous or inflammatory. Demographic data like age and sex were recorded. The type of operation done, findings at surgery, and the histopathology of the resected specimen were all recorded. The time taken for the pathology department to process the biopsy and resected specimens was also recorded. Results. 120 patients with CRC were seen over the study period of 5 years (2009–2013) giving an average of 24 patients per annum. The male : female ratio was 1 : 1.14. 86 (71.7%) patients had rectal cancer while the remaining 34 (28.3%) had colon cancer. Most of the colon cancer cases were in the 51–60 age group. The rectum : colon ratio was 2.5 : 1.31% of the patients were 40 years and below. 37% of those with rectal cancer were 40 years and below. 50% of resected specimens were Duke’s B and above. 45% of patients had tumors with unfavorable grade or biology (mucinous 21.7%, signet ring 8.3%, and poorly differentiated 15%). Only 24% of patients below 40 years and 41% of those above 40 years with confirmed rectal carcinoma presented for operation. Conclusion. Advanced tumors at presentation may not always be as a result of late presentation. Unusual aggressiveness of the tumors may lead to rapid progression of the disease. Increasing incidence in younger patients makes abdominoperineal excision of the rectum difficult for such patients to accept. David O. Irabor, O. Oludolapo Afuwape, and Omobolaji O. Ayandipo Copyright © 2014 David O. Irabor et al. All rights reserved. A Review of the Potential Utility of Mycophenolate Mofetil as a Cancer Therapeutic Mon, 07 Jul 2014 00:00:00 +0000 Tumor cells adapt to their high metabolic state by increasing energy production. To this end, current efforts in molecular cancer therapeutics have been focused on signaling pathways that modulate cellular metabolism. However, targeting such signaling pathways is challenging due to heterogeneity of tumors and recurrent oncogenic mutations. A critical need remains to develop antitumor drugs that target tumor specific pathways. Here, we discuss an energy metabolic pathway that is preferentially activated in several cancers as a potential target for molecular cancer therapy. In vitro studies have revealed that many cancer cells synthesize guanosine triphosphate (GTP), via the de novo purine nucleotide synthesis pathway by upregulating the rate limiting enzyme of this pathway, inosine monophosphate dehydrogenase (IMPDH). Non-proliferating cells use an alternative purine nucleotide synthesis pathway, the salvage pathway, to synthesize GTP. These observations pose IMPDH as a potential target to suppress tumor cell growth. The IMPDH inhibitor, mycophenolate mofetil (MMF), is an FDA-approved immunosuppressive drug. Accumulating evidence shows that, in addition to its immunosuppressive effects, MMF also has antitumor effects via IMPDH inhibition in vitro and in vivo. Here, we review the literature on IMPDH as related to tumorigenesis and the use of MMF as a potential antitumor drug. Nazanin Majd, Kazutaka Sumita, Hirofumi Yoshino, Dillon Chen, Jumpei Terakawa, Takiko Daikoku, Satoshi Kofuji, Richard Curry, Trisha M. Wise-Draper, Ronald E. Warnick, Jessica Guarnaschelli, and Atsuo T. Sasaki Copyright © 2014 Nazanin Majd et al. All rights reserved. A Phase IV Clinical Trial of Patients with Solid Tumors Receiving Lenograstim as Primary Prophylaxis for Chemotherapy-Induced Neutropenia, in a Docetaxel-Based Regimen Sun, 06 Apr 2014 00:00:00 +0000 Docetaxel-based chemotherapy regimens have substantially improved survival and recurrence rates for cancer patients. Safety profile of docetaxel regimens includes toxicities, particularly a high risk of neutropenia and febrile neutropenia. Granotax was a prospective, open label, multicentre, national phase IV study that evaluated the incidence and severity of neutropenia in adult patients with solid tumors being treated with a docetaxel-based regimen while receiving the GCSF lenograstim. Among the 394 enrolled patients the incidence of grade 3-4 neutropenia was 16.2% and of febrile neutropenia was 1.5%, far lower than the reported 85–100% and 30–40% incidence without G-CSFs. A total of 68 patients (17.3%) were reported to have experienced at least one grade 3-4 adverse event during the study. Two (0.5%) patients and 32 (8.1%) patients had dose delayed due to febrile neutropenia and neutropenia, respectively. Four (1.0%) patients and 32 (8.1%) patients had a dose changed due to febrile neutropenia and neutropenia, respectively. The low incidence of adverse effects and chemotherapy dose changes, delays, and withdrawals supports the use of lenograstim as effective primary prophylaxis in South African patients being treated with a docetaxel-based regimen. Furthermore, lenograstim may increase the patient’s exposure to chemotherapy allowing patients to receive optimal dosing and duration of treatment, benefitting survival. Samuel J. Fourie, Alicia McMaster, Rashem Mothilal, and Keith I. Maart Copyright © 2014 Samuel J. Fourie et al. All rights reserved. Implications of Post-LLETZ “Treatment Failure” for Further Management of HIV-Infected Women Tue, 11 Mar 2014 00:00:00 +0000 Background. Since the preconisation presence of high-risk human papillomavirus (HR-HPV) is the main determinant of the risk of progression of preinvasive lesions; the state of the excision margins could be of less importance. Relatively little is known about the effect of human immunodeficiency virus (HIV) infection on the relation between the states of the excision margins. Methods. We compared 120 HIV-infected and 139 HIV-uninfected women who underwent a hysterectomy after large loop excision of the transformation zone (LLETZ) for abnormal Pap smear. Results. The excision margins had been reported negative in 21.7% of infected and 7.8% of uninfected cases (). Three (11.5%) of 26 negative margins in HIV-infected and 2 (18.2) out of HIV-uninfected cases were falsely negative as evidenced on hysterectomy specimens (). The persistence rate of the initial lesion was similar in both groups (). The persistence rate with highly active antiretroviral treatment (HAART) was similar to untreated patients (). The progression rate from low-grade to high-grade preinvasive lesions was higher in HIV-infected than HIV-uninfected women (). Conclusion. HIV-infected women with incomplete excision margins after LLETZ are at higher risk of progression of residual preneoplastic lesions. Louis-Jacques van Bogaert Copyright © 2014 Louis-Jacques van Bogaert. All rights reserved. Tetracycline and Glutathione Inhibit Matrix Metalloproteinase Activity: An In Vitro Study Using Culture Supernatants of L929 and Dalton Lymphoma Cell Lines Sun, 29 Dec 2013 11:54:20 +0000 Tetracycline and glutathione inhibited the protease activities of matrix metalloproteinase-2 and matrix metalloproteinase-9 expressed by mouse fibrosarcoma cells (L929) and Dalton lymphoma cells, respectively. The inhibitory activity of the tetracycline may be due to its ability to chelate metal ions such as calcium and zinc. Gelatin-zymography technique was used to demonstrate the inhibitory activity of both tetracycline and glutathione. The intensity of the bands corresponding to metalloproteinase activity in zymography gel was reduced in the presence of 50–100 μg/mL of tetracycline. The presence of 10–100 μg/mL of tetracycline in the medium increased the adherence of L929 cancer cells. These results clearly indicate the antimetastatic property of tetracycline. Reduced glutathione, a compound which is produced endogenously by the cells to maintain the redox status, was shown to inhibit the matrix metalloproteinase activity (in vitro). Therefore, it is assumed that decreased glutathione levels in synovial fluids or plasma might increase the activity of MMP. Reduced glutathione at 100 μg/mL inhibited the metalloproteinase activity in gelatin-zymographic gel. As both tetracycline and glutathione exhibited an inhibitory effect on matrix metalloproteinase activity, it was of great interest to check their clinical effects on various MMP associated pathological conditions such as cancer metastasis and arthritis. Here we report that tetracycline and reduced glutathione inhibited the activity of MMP2 completely and activity of MMP9 partly. Gajanan Kendre, Rahul Raghavan, Sanith Cheriyamundath, and Joseph Madassery Copyright © 2013 Gajanan Kendre et al. All rights reserved. Taxpas: Epidemiological and Survival Data in Breast Cancer Patients Treated with a Docetaxel-Based Chemotherapy Regimen in South Africa Wed, 11 Dec 2013 09:27:20 +0000 Breast cancer is the leading cancer among South African women. There is limited South African epidemiological data on triple-negative breast cancer (TNBC). Taxpas was a nonrandomized observational survey conducted in multiple centres in South Africa from April 2004 to December 2010. 1632 female patients diagnosed with breast cancer, with a median age of 51 years, were enrolled in the survey. Patients were treated on a docetaxel-based chemotherapy regimen. The objective of the study was to assess epidemiological data and survival data. The incidence of TNBC was 14%. The one-year survival rate for the total cohort was 84%. The one-year survival rate for patients with early stage and metastatic breast cancer was recorded as 94% and 65%, respectively. Patients with TNBC stage III (all ages) and stage IV (≤50 years) had statistically significant worse 1-year survival rate compared to N-TNBC patients of the same age and stages. Conclusion. The incidence of TNBC in South Africa which is 14% is comparable to global incidence. The 1-year survival data for certain subgroups supports the literature saying that TNBC carries a worse prognosis compared to N-TNBC. Women ≤50 years diagnosed with late stage TNBC carried the worst prognosis in this survey. Shun Devan Moodley, Alicia McMaster, and Rashem Mothilal Copyright © 2013 Shun Devan Moodley et al. All rights reserved. Fecal Collection and Stabilization Methods for Improved Fecal DNA Test for Colorectal Cancer in a Screening Setting Sun, 24 Nov 2013 10:12:52 +0000 Early detection of CRC and adenomas reduces CRC-related mortality. The optimal screening test for CRC is still a subject of debate, and molecular stool sample analysis could provide a valid alternative to conventional methods in terms of compliance and practicability. Seven fecal DNA storage systems were evaluated in two successive phases. In the first phase of the study was selected the preservative buffer able to ensure the best human DNA recovery. In the second phase was evaluated human DNA stability, amplificability and integrity in DNA extracted from selected buffer. Results showed that the best performance was obtained in samples stored in 100 mM EDTA buffer and Genefec buffer. Likewise buffer addition yielded a significant increase in DNA stability and integrity without PCR inhibition, compared to the matched aliquots with no buffer added. Our study shows that samples collected in stabilization solution stabilize DNA so that intact nucleic acids, are more effectively detectable in the molecular assay. DNA buffer preservation and storage conditions could be useful to guarantee the most consistent yield in human DNA. Stabilization buffer addition to stool samples prior to transport presents an easily implemented solution that appears to be highly effective. Overall DNA extracted from faeces preserved in preservative buffer can feasibility been used for molecular analysis leading to an increase of assay sensitivity. Francesca Maria Carozzi and Cristina Sani Copyright © 2013 Francesca Maria Carozzi and Cristina Sani. All rights reserved. Bleomycin-Induced Lung Injury Tue, 08 Oct 2013 13:51:39 +0000 Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as germinative tumors and Hodgkin’s lymphoma. The major limitation of bleomycin therapy is pulmonary toxicity, which can be life threatening in up to 10% of patients receiving the drug. The mechanism of bleomycin-induced pneumonitis (BIP) involves oxidative damage, relative deficiency of the deactivating enzyme bleomycin hydrolase, genetic susceptibility, and the elaboration of inflammatory cytokines. Ultimately, BIP can progress to lung fibrosis. The diagnosis of BIP is established by the combination of systemic symptoms, radiological and histological findings, and respiratory function tests abnormalities, while other disorders should be excluded. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. In general, the clinical picture is extremely complex. A greater understanding of the BIP pathogenesis may lead to the development of new agents capable of preventing or even treating the injury already present. Physicians who prescribe bleomycin must be aware of the potential pulmonary toxicity, especially in the presence of risk factors. This review will focus on BIP, mainly regarding recent advances and perspectives in diagnosis and treatment. Tomás Reinert, Clarissa Serodio da Rocha Baldotto, Frederico Arthur Pereira Nunes, and Adriana Alves de Souza Scheliga Copyright © 2013 Tomás Reinert et al. All rights reserved. The Effect of Hydroxybenzoate Lithium Complexes in Inducing Apoptosis in HT-1080 Human Fibrosarcoma Cells Thu, 22 Aug 2013 12:47:39 +0000 There has been a growing interest in the beneficial effects of simple phenolic acids and their ability to exhibit various biological activities. The aim of this study was to assess in vitro biological activities of 2-, 3-, and 4-hydroxybenzoate lithium (HBLi) complexes on HT-1080 human fibrosarcoma cells by methods of using a metabolic activity assay, immunochemical and morphological techniques. Results showed that HBLi complexes exert their cytotoxic activities in a concentration- and chemical structure-dependent manner in the following order: 4-HBLi > 3-HBLi > 2-HBLi. Flow cytometry displayed evidence of apoptosis induced by 3-HBLi (21.8%) and 4-HBLi (33.2%). These results were verified by SEM, which revealed the formation of apoptotic bodies. In addition, these 3-HBLi and 4-HBLi caused an increase in HT-1080 cell cycle arrest in G0/G1 phase when compared to the controls (25% and 30.6%, resp.) when cells were treated with 6 mM for 24 hours. Immunochemical studies related to the molecular mechanism of apoptosis indicated that HBLi complexes downregulated the expression of Bcl-2 and upregulated Bax, p53, and caspases-3 in a concentration-dependent manner. HBLi complexes lowered Bcl-2/Bax ratios and induced the expression of p53 and caspase-3. These results suggest that HBLi complexes may exert their apoptotic effects through mitochondrial-mediated, caspase-dependent, apoptotic mechanisms. Jassem G. Mahdi, Eamon J. Mahdi, Amal Al-Hazzaa, and Chris J. Pepper Copyright © 2013 Jassem G. Mahdi et al. All rights reserved. Derailing the UPS of Protein Turnover in Cancer and other Human Diseases Mon, 05 Aug 2013 11:43:50 +0000 Protein modifications by the covalent linkage of ubiquitin have significant involvement in many cellular processes, including stress response, oncogenesis, viral infection, transcription, protein turnover, organelle biogenesis, DNA repair, cellular differentiation, and cell cycle control. We provide a brief overview of the fundamentals of the regulation of protein turnover by the ubiquitin-proteasome pathway and discuss new therapeutic strategies that aim to mitigate the deleterious effects of its dysregulation in cancer and other human disease pathophysiology. Jit Kong Cheong and Stephen I-Hong Hsu Copyright © 2013 Jit Kong Cheong and Stephen I-Hong Hsu. All rights reserved. Tumour Angiogenesis: A Growth Area—From John Hunter to Judah Folkman and Beyond Sun, 28 Jul 2013 08:40:02 +0000 Angiogenesis is the growth of new blood vessels in the body. Abnormal angiogenesis is recognised as a “common denominator” in many disease processes, and the development of angiogenesis inhibitors holds great hope in the ongoing battle against cancer. The field of angiogenesis has roots in the Hunterian era of the late eighteenth century but did not begin to blossom until the early 1970s when the then controversial findings and conclusions of Judah Folkman, the “father of angiogenesis,” were first published. There were only 65 publications with angiogenesis in the title in the 10 years after Folkman first proposed the idea of tumour angiogenesis, compared to over 9,000 publications from the year 2000 to 2010. In this review we will explore the voyage of discovery from the first observations of John Hunter in the eighteenth century, via the struggle faced by Folkman to prove the importance of angiogenesis, and finally how his determination has led to modern angiogenesis inhibitors being used in everyday clinical practice. J. A. Stephenson, J. C. Goddard, O. Al-Taan, A. R. Dennison, and B. Morgan Copyright © 2013 J. A. Stephenson et al. All rights reserved. Correlating Pap Smear Results and Colposcopy-Directed Large Loop Excision of the Transformation Zone Histopathology in HIV-Infected and HIV-Uninfected Women: A Case-Control Study in South Africa Wed, 24 Jul 2013 08:30:06 +0000 Background. In low-resource settings (LRS) with high HIV/AIDS and cervical cancer rates, new screening strategies face many logistic hurdles. Since cytology is there to stay, at least in the median-term future, it is important to assess to what extent HIV-HPV coinfection impacts the accuracy of screening methods and strategies. Methods. We audited the correlation between cytological diagnosis of minimal abnormality (CIN1), CIN2+, or cancer and the histological diagnosis of colposcopy-directed large loop excision of the transformation zone of 399 HIV-uninfected controls and 389 HIV-infected cases. Results. The average age at diagnosis of CIN2+ of the cases was 4.2 years younger than controls (). The endpoint used to assess the accuracy of cytology was minimal cytological abnormality (≤CIN1/LGSIL). The sensitivity, specificity, and negative and positive predictive values were 92.7, 18.5, 45.1, and 77.9%, respectively. The overall ratio of discordance/concordance between cytology and histology was similar in both groups. Conclusion. In LRS, where rapid-HPV testing is not yet part of screening algorithms, a cytological diagnosis of minimal abnormality requires visual inspection and treatment of visualized lesions especially in HIV-infected women aged 30 years. The cytological endpoint of accuracy should be set low to avoid false negative smears. Louis-J. van Bogaert Copyright © 2013 Louis-J. van Bogaert. All rights reserved. The Breakage-Fusion-Bridge Cycle Producing MLL Amplification in a Case of Myelodysplastic Syndrome Thu, 18 Jul 2013 08:51:16 +0000 Telomere loss may lead to chromosomal instability via the breakage-fusion-bridge (BFB) cycle which can result in genetic amplification and the formation of ring and dicentric chromosomes. This cycle continues until stable chromosomes are formed. The case of a 72-year-old female with refractory anaemia with excess blasts type 2 illustrates these events. Conventional cytogenetics produced a complex karyotype which included unstable abnormalities of chromosomes 11, 12, and 15. Fluorescence in situ hybridization (FISH) analyses including multicolor-FISH (M-FISH) and multicolor-banding (M-BAND) revealed multiple clonal populations with 5 copies of MLL on either a ring chromosome composed entirely of chromosome 11 material or a derivative chromosome composed of chromosomes 11, 12, and 15. The FISH results also clarified the likely evolution of the karyotypic complexity. The simplest cell line contained a dic(12;15) in addition to copy number aberrations that are typical of MDS or AML. As the disease progressed, a ring 11 was formed. Subsequently, the ring 11 appears to have unwound and inserted itself into the dic(12;15) chromosome followed by an inversion of the derivative chromosome, producing a der(11;15;12). Telomeric loss and BFB cycles appear to have played an important role in the chromosomal rearrangements and clonal evolution demonstrated in the karyotype. Lan Ta, Adrian Zordan, Bruce Mercer, Lynda J. Campbell, and Ruth N. MacKinnon Copyright © 2013 Lan Ta et al. All rights reserved. Targeting Oncogene-Induced Autophagy: A New Approach in Cancer Therapy? Wed, 19 Jun 2013 16:59:35 +0000 Autophagy is a tightly controlled self-degradation process utilised by cells to sustain cellular homeostasis and to support cell survival in response to metabolic stress and starvation. Thus, autophagy plays a critical role in promoting cell integrity and maintaining proper function of cellular processes. Defects in autophagy, however, can have drastic implications in human health and diseases, including cancer. Described as a double-edged sword in the context of cancer, autophagy can act as both suppressor and facilitator of tumorigenesis. As such, defining the precise role of autophagy in a multistep event like cancer progression can be complex. Recent findings have implicated a role for components of the autophagy pathway in oncogene-mediated cell transformation, tumour growth, and survival. Notably, aggressive cancers driven by Ras oncoproteins rely on autophagy to sustain a reprogrammed mitochondrial metabolic signature and evade cell death. In this review, we summarize our current understanding of the role of oncogene-induced autophagy in cancer progression and discuss how modulators of autophagic responses can bring about therapeutic benefit and eradication of a subset of cancers that are addicted to this ancient recycling machinery. Fuquan Zhang and Jit Kong Cheong Copyright © 2013 Fuquan Zhang and Jit Kong Cheong. All rights reserved. Clinical Finding and Thyroid Function in Women with Struma Ovarii Thu, 23 May 2013 13:46:56 +0000 Background. Struma ovarii (SO) is a variant of dermoid tumors which completely or mainly composed of thyroid tissues. Objective. We report our experience in the diagnosis and thyroid function of patients with SO in our hospital and also review the management and treatment option of this tumor. Materials and Methods. Between 2000 and 2012, 15 consecutive females with SO who were presented to our hospital were fully assessed. All women had histologically confirmed struma ovarii. The medical records of all patients including presenting symptoms, CT scan finding, and hormonal levels were collected for final analysis. Results. Average patient age was 36.6 years (ranging from 21 to 69). The mean ± SDs of serum TSH, T4, and T3 were  mUI/mL,  ng/dL, and  ng/dL, respectively. The value of TSH was lower than normal value in 26.7%. Also, antithyroglobulin and anti-TPO were positive in 2 and one cases, respectively. Conclusion. Based on our data, it is more likely to see a disturbance in serum values of thyroid function test in women with SO. Ali Hosseini and Aida Moeini Copyright © 2013 Ali Hosseini and Aida Moeini. All rights reserved.