Journal of Analytical Oncology

‘Hygienic’ Lymphocytes Convey Increased Cancer Risk
Pages 113-121
Tatiana Levkovich, Theofilos Poutahidis, Kelsey Cappelle, Mark B. Smith, Allison Perrotta, Eric J. Alm and Susan E. Erdman
Published: 12 August 2014

Abstract: Risk of developing inflammation-associated cancers has increased in industrialized countries during the past 30 years. One possible explanation is societal hygiene practices with use of antibiotics and Caesarian births that provide too few early life exposures of beneficial microbes. Building upon a ‘hygiene hypothesis’ model whereby prior microbial exposures lead to beneficial changes in CD4+ lymphocytes, here we use an adoptive cell transfer model and find that too few prior microbe exposures alternatively result in increased inflammation-associated cancer growth in susceptible recipient mice. Specifically, purified CD4+ lymphocytes collected from ‘restricted flora’ donors increases multiplicity and features of malignancy in intestinal polyps of recipient ApcMin/+ mice, coincident with increased inflammatory cell infiltrates and instability of the intestinal microbiota. We conclude that while a competent immune system serves to maintain intestinal homeostasis and good health, under hygienic rearing conditions CD4+ lymphocytes instead exacerbate inflammation-associated tumorigenesis, subsequently contributing to more frequent cancers in industrialized societies.

Keywords: Hygiene, ApcMin/+, cancer, inflammation, microbiome.
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99mTc-Labeled Bevacizumab via HYNIC for Imaging of Melanoma
Pages 53-64
Ximena Camacho, María Fernanda García, Victoria Calzada, Marcelo Fernández, Omar Alonso, Juan Pablo Gambini, Rodrigo Barbosa de Aguiar, Camila Maria Longo Machado, Roger Chammas, Williams Porcal and Pablo Cabral
Published: 18 February 2014

Abstract: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumour-induced angiogenesis in several types, including melanoma. Bevacizumab, a monoclonal antibody anti-VEGF, could be used as an imaging tool in clinical studies. The aim of this study was to radiolabeled Bevacizumab with 99mTc and evaluate it in vivo imaging properties. Bevacizumab was derivatized with the activated ester succinimidyl-hydrazinonicotinamide hydrochloride (Suc-HYNIC) as a bifunctional coupling agent. A mixture of Tricine/SnCl2.2H2O was added to Bevacizumab-HYNIC and radiolabeled with 99mTcO4-. The radiochemical stability of the radiolabeled sntibody was assessed. Biodistribution studies and SPECT-CT imaging were evaluated in healthy and tumor-bearing C57BL/6J mice at 1, 4 and 24 h (n =5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable over 24 h in solution and serum. In vivo biodistribution studies revealed tumor-to-muscle ratios of 99mTc-HYNIC-Bevacizumab was 9.28, 17.19 and 8.51 at 1, 4 and 24 h p.i. SPECT/CT imaging of tumor-bearing C57BL/6J mice showed tumor selective uptake of 99mTc-HYNIC-Bevacizumab. 99mTc-HYNIC-Bevacizumab could become a potential radiopharmaceutical to evaluate the expression of vascular endothelial growth factor (VEGF) in solid tumors and could be seen as a clinic tool for the screening of solid tumors that might respond to the Bevacizumab chemotherapy.

Keywords: Melanoma, Angiogenesis, Bevacizumab, HYNIC, organic synthesis, technetium-99m.
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A Case Report of Visual Disturbance Caused by Thrombosis of the Superior Sagittal Sinus
Pages 41-45
Daiki Taniyama, Tsuyoshi Torii, Junichiro Kuga, Yoriko Dodo, Hitomi Tanaka, Yoshimasa Sueda and Kiyomi Taniyama
Published: 31 January 2014Open Access

Abstract: Superior sagittal sinus thrombosis is a rare condition caused by several diseases including malignancy. Major symptoms include headache, seizure, and motor weakness. Ocular sign is a minor symptom. The present case had visual disturbance caused by thrombosis of the superior sagittal sinus, which is an extremely rare case that was treated successfully by our team.

Keywords: Cerebral venous thrombosis, Optic papilla, Congestion, Lung, Hypercoagulopathy, Squamous cell carcinoma..
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A Case of Sigmoid Colon Cancer in which Somatic Pain was Rapidly Alleviated after Panitumumab Administration Despite Tumor Progression
Pages 38-4188x31
Shu Yuasa, Megumi Kabeya, Ryuichi Furuta, Satoshi Hibi, Chiaki Koga, Seiji Nagao and Kenji Ina

Published: 05 April 2016

Abstract: We present a 72-year-old woman with sigmoid colon cancer in whom the somatic pain was alleviated rapidly after the administration of anti-epidermal growth factor antibodies. Our patient had received 4 cycles of FOLFIRI therapy (irinotecan, 5-fluorouracil, and leucovorin) in combination with panitumumab (Pmab) for the treatment of unresectable primary cancer accompanied with multiple liver metastases and peritonitis carcinomatosa. As grade 3 paronychia eventually occurred, chemotherapy was stopped. After recovery of the grade 3 paronychia, Pmab was re-introduced and administered every alternate cycle to reduce the extent of adverse events. The patient had complained of somatic pain in the lower right abdomen just before re-initiating Pmab administration. The pain intensity decreased immediately after the administration of Pmab. On the next day her pain had remarkably alleviated and she was free from pain for a week. This phenomenon was repeatedly observed. After the re-introduction of Pmab, tumor response was evaluated on computed tomography, which showed progressive disease. We demonstrated that Pmab was effective in the alleviation of somatic pain, although the size of the tumors gradually increased.

Keywords: Panitumumab, anti-EGFR antibody, somatic pain, colon cancer.
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A DNA Vaccine Targeting the Fetal Liver Kinase-1 (Flk-1) can Activate the Special CD8+ T Cell and Inhibit the Metastasis of Orthotopic Lewis Lung Cancer Model
Pages 233-240
Xin Liu, Yan Chen, Zhi Ping Wu, Cong Guo Jin, Xiao Qun Chen, Jia Li, Yong Chun Zhou and Xi Cai Wang
DOI: http://dx.doi.org/10.6000/1927-7229.2013.02.04.6

Published: 31 October 2013

Abstract: Lung cancer is the leading cause of cancer related deaths and need new more effective therapies. In this study, we investigated the anti-tumor effect of recombinant orally DNA vaccine delivered by attenuated S.typhimurium strain SL3261 (aroA mutant) targeting vascular endothelial growth factor receptor (VEGFR-2), also known as fetal liver kinase-1 (Flk-1) in mouse. The cDNA of extracellular domains (ECD) of VEGFR-2 (Flk-1ECD) was amplified by RT-PCR and cloned into the pcDNA3.1 (+) vector, then transformed to the attenuated S.typhimurium strain to construct the oral DNA vaccine. Then pcDNA3.1-Flk-1ECD was successfully transfected into COS-7 cells and the recombinant protein was detected by Western blot. The effect of the oral DNA vaccine was analyzed by flow cytometry (FCM) analysis and cytotoxicity assay. For mimic the local and regional growth pattern seen in lung cancer patients, the effect of the oral DNA vaccine on tumor growth and metastasis was analyzed by orthotopic cancer cells challenge in vivo. The results demonstrated that the oral DNA vaccine can overcome peripheral immune tolerance, and generated Flk-1- specific CD8+ cytotoxic T cell response. Moreover, this oral DNA vaccine could effectively reduce tumor growth, metastasis and increase the survival. It indicated that the oral VEGFR2 DNA vaccine encoding Flk-1ECD delivered by salmonella might act a potential strategy for immunotherapy of lung cancers.

Keywords: Lung cancer, VEGFR-2, oral vaccine, angiogenesis, metastasis, orthotopic.
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