Journal of Cancer Research The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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.