Secondary Precursor T-Cell Lymphoblastic Lymphoma Following Precursor B-cell Acute Lymphoblastic Leukemia: A Case Report and Review of the Literature
Pages 117-122
Jenny L. Smith, Albert Kheradpour, Craig W. Zuppan, Jun Wang, Rhett P. Ketterling and Edward H. Rowsell

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.02.6

Published: 08 May 2014

Abstract: Although relapse of lymphoma/leukemia is not uncommon, sequential development of a second lymphoma/leukemia of a different cell lineage is rare. We report the case of a 3-year-old girl who initially presented with precursor B-cell acute lymphoblastic leukemia (B-ALL), characterized by a cryptic t(12;21) with associated ETV6/RUNX1 fusion, an 11q (MLL) deletion, and a balanced inv(2)(q31q37). She was successfully treated but five years later developedthymicprecursor T-cell lymphoblastic lymphoma (T-LBL) expressing a completely different phenotypic profile. Fluorescence in situ hybridization testing identified a MLL rearrangement but indicated no ETV6/RUNX1 fusion. Although the marrow was uninvolved, aspirates evaluated by chromosome studies revealed the same inv(2q), suggesting a constitutional abnormality distinct from the somatic alterations associated with her B-ALL and T-LBL. This raisesthe possibilityof a potential tumor suppressor gene or proto-oncogene residing in the region of the inversion breakpoints which could contribute to predisposition to the development of lymphoblastic leukemias/lymphomas. While secondary leukemia may emerge as a therapy-related process and the presence of an MLL rearrangement in the T-LBL represents an interesting abnormality in this regard,athymicpresentation would be exceedingly unusual. To our knowledge, this is the first reported case of B-ALL followed by an apparently genetically unrelatedT-LBL.

ABC Transporters: Maintenance of the Cancer Stem Cell Phenotype
Pages 283-288
Wei Zhang and Li-Wu Fu

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.01.1

Published: 31 January 2014

Abstract: The poor therapeutic response to anti-cancer treatment and inferior prognosis of carcinoma primarily result from cancer stem cells (CSCs), which initiate and maintain tumors. Recent studies have demonstrated that the molecular phenotype of CSCs mainly consists of multidrug resistance (MDR), self-renewal, multi-lineage differentiation potential (pluripotency) and tumorigenicity. Intriguingly, ATP-binding cassette (ABC) membrane transporters are highly expressed in CSCs compared to non-CSCs, and recent evidence has highlighted a link between ABC transporters and the CSC phenotype. Understanding the relationship between CSCs and ABC transporters is important as this could lead to the development of more efficacious treatment regimens. Thus, in this article, we will mainly review the relationships between ABC transporters and the phenotype of CSCs.

Conventional Oral Systemic Chemotherapy for Postoperative Hepatocellular Carcinoma
Pages 283-288
Jian-Hong Zhong and Le-Qun Li

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.01.2

Published: 31 January 2014

Abstract: Background:The findings of randomized clinical trials (RCTs) about the efficacy of adjuvant conventional oral systemic chemotherapy (COSC) for patients with hepatocellular carcinoma (HCC) after curative hepatic resection (HR) are contradictory. Therefore, a systematic review of clinical trials is needed to evaluate the clinical efficacy of adjuvant COSC.

Methods:Sources such as MEDLINE, EMBASE and the Cochrane Library were systematically searched.All clinical trials comparing curative HR with HR plus COSC for HCC were identified. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results:Five RCTs and one non-RCT involving a total of 461 patients were included. No treatment-related deaths were reported in the including trials. The adverse effects of COSC were generally mild. However, included studies and meta-analysis showed that adjuvant COSC did not demonstrate statistically significant improvement for the 1-, 3-, and 5-year overall survival. For the 1-, 3-, and 5-year tumor recurrence and recurrence-free survival rates, adjuvant COSC also did not show statistically significant less incidence.

Conclusion:Adjuvant COSC provides no survival benefits for HCC patients after curative HR. Considering the efficacy of sorafenib for advanced HCC and the results of this systematic review, no more trials should be carried out to explore the efficacy of adjuvant COSC.

EGCG Suppresses Melanoma Tumor Angiogenesis and Growth without Affecting Angiogenesis and VEGF Expression in the Heart and Skeletal Muscles in Mice
Pages 19-29
Kevan B. Tucker, Kristina L. Makey, Edmund Chinchar, Min Huang, Natale Sheehan, Srinivasan Vijayakumar and Jian-Wei Gu

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.01.3

Published: 31 January 2014

Abstract: Melanoma is a highly malignant cancer with a potent capacity to metastasize distantly and has a higher mortality. There is no effective therapy for high risk melanoma patients to prevent relapse or distant metastasis. Therefore effective chemoprevention strategies are needed. The present study mainly evaluates the effects of EGCG on melanoma angiogenesis, growth, and capillary density (CD) in the heart and skeletal muscles of mice. 5 x 10^5 B16F10 cells were inoculated into the right proximal dorsal of the back in the eight week old male mice (n=12). Then, 6 mice received EGCG at 50–100 mg/kg/d in drinking water for 4 weeks and 6 control mice received drinking water only. Tumor size was monitored using dial calipers. At the end of the experiment, blood samples, tumors, hearts, and limb muscles were collected and measured for VEGF expression using ELISA and capillary density (CD) using CD31 immunohistochemistry. Compared to the control, EGCG treatment significantly reduced tumor weight (2.9±0.5 vs. 5.9±1.1 g; P<0.01; n=6), melanoma CD (117±9 vs. 167±23; P<0.01), and melanoma VEGF expression (32±1.5 vs. 42±2 pg/mg; P < 0.01), respectively. Also EGCG had no effects on body weight, heart weight, angiogenesis or VEGF expression in the heart and skeletal muscle of mice. EGCG (20-50 µg/ml) significantly inhibited the proliferation, migration, VEGF expression, and the activation of HIF-1α and NFκB in cultured B16F10 cells, respectively. These findings support the hypothesis that EGCG, a major green tea polyphenol, directly targets tumor cells and tumor vasculature, thereby inhibiting tumor growth, proliferation, migration, and angiogenesis of melanoma, and that the down-regulation of VEGF expression by EGCG is associated with the inhibition of HIF-1α and NFκB activation. EGCG has great potential as a chemopreventive agent because it has no effect on angiogenesis in normal tissue and has low toxicity.

Intraparenchymal chordoid MeningiomaAfter Radiotherapy for Hodgkin Lymphoma: A Case Report and Review of the Literatur
Pages 30-41
Mustafa Efendioglu, Recep Basaran, Dogan Gundogan, Fatih Han Bolukbası, Mustafa Kaksi, Aydin Sav and Tuncay Kaner

DOI: http://dx.doi.org/10.6000/1929-2279.2014.03.01.4

Published: 31 January 2014

Abstract: Objective: Hodgkin lymphoma can be treated by radiotherapy or chemotherapy alone or combined. Meningiomas account for 1-4.2% of all primary intracranial tumors in children, and chordoid meningioma is a very rare subtype. In this study, we investigated a case of an intraparenchymal chordoid meningioma that developed during the early stage in a patient with Hodgkin lymphoma who had been treated with radiotherapy.

Case: A 10-year-old male patient was diagnosed with Hodgkin lymphoma and was treated with a combination of radiotherapy and chemotherapy. He presented at our emergency service 6 years later. He had a fever and was suffering from discomfort and insignificant left hemiparesis (4/5). Contrast-enhanced cranial magnetic resonance imaging (MRI) showed a mass in the right temporoparietal region. The intracranial lesion was surgically excised. The tumor was identified as a WHO grade 2 chordoid meningioma by the pathological examination. The Ki-67 proliferation index was found to be 20-25%.

Conclusion: Surgeons must remember that radiation-associated meningiomas may occur in the early stage of the treatment as well as in the late stage. Young patients with grade 2 chordoid meningiomas must be followed-up in case of recurrence, and tumors with high Ki-67 indexes are highly expected to relapse.