Oncology Research 19(8-9) Abstracts

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Oncology Research, Vol. 19, pp. 375-380–, 2011
0965-0407/11 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504011X13123323849636
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Prostate-Specific Antigen Gene Expression and Telomerase Activity in Breast Cancer Patients: Possible Relationship to Steroid Hormone Receptors

A. Mohajeri,*† N. Zarghami,* M. Pourhasan Moghadam,* B. Alani,‡ V. Montazeri,§ A. Baiat,§ and A. Fekhrjou¶

*Department of Clinical Biochemistry and RIA, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
†Department of Research & Development, Zahravi Pharmaceutical Company, Tabriz, Iran
‡Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
§Department of Surgery, Imam Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
¶Department of Pathology, Imam Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

Breast cancer, the most prevalent cancer among women, is a steroid hormone receptor-dependent cancer. Recently, it has been shown that telomerase and prostate-specific antigen (PSA) gene expressions are under control of steroid hormone receptors. The aim of this study was to investigate the relationship between telomerase activity and PSA gene expression with steroid hormone receptors in breast cancer patients. This study consisted of 50 women with breast benign tumors and 50 malignant (invasive) tumors. Telomerase activity was measured in tumor cytosol of samples by telomeric repeat amplification protocol (TRAP) assay. PSA protein and its mRNA expression were measured using ultrasensitive immunoassay and RT-PCR technique in all tumor tissues, respectively. Estrogen and progesterone receptors were stained using immunohistochemistry in tumor tissues. Telomerase activity was detected in all of the invasive breast cancer tissues. The difference of relative telomerase activity (RTA) values between stages and grades were statistically significant (p < 0.05). The PSA mRNA was detected only in benign tumors and stage I and grade I malignant tumor cytosol. Difference of tumor cytosol PSA levels between the cases and control groups and also between all grades and stages of diseases were significant (p < 0.05). There was an inverse significant correlation between the RTA and PSA protein levels in the case groups (r = −0.42, p < 0.05). There was a statistically significant difference between ER/PR with PSA level and telomerase activity in tumor tissues (p < 0.05). It is speculated that differential expression of PSA and telomerase genes in breast tumors are under control of steroid hormone receptors and could be used as a target for treatment in the future.

Key words: Prostate-specific antigen (PSA); Telomerase; Gene expression; Breast cancer

Address correspondence to N. Zarghami, M.D., Ph.D., Department of Clinical Biochemistry and RIA, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Tel: +98-4113363234, ext. 241; Fax: +98-4113363231; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 381–390, 2011
0965-0407/11 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504011X13123323849654
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Expression of DNA Damage Checkpoint Proteins and Prognostic Implication in Metastatic Brain Tumors

Ho Jun Seol,*1Hae Yong Yoo,†1Juyoun Jin,*†‡1Kyeung Min Joo,†‡§ Hyeong-Seok Kim,*†‡ Su Jin Yoon,† Seung Ho Choi,† Yonghyun Kim,*†‡ Hong Ryull Pyo,¶ Do-Hoon Lim,¶ Wook Kim,# Hong-Duck Um,** Jong Hyun Kim,* Jung-II Lee,* and Do-Hyun Nam*†‡

*Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
†Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
‡Cancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
§Department of Anatomy, Seoul National University College of Medicine, Seoul, South Korea
¶Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
#Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea
**Laboratory of Radiation Tumor Physiology, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea

The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, DNA damage checkpoint signaling pathway activation after irradiation has received increasing attention. The association between the expression levels and survival outcome was evaluated to find possible therapeutic targets in brain metastasis. Radiosensitivity of human non-small cell lung cancer cell lines was determined by checking their viability after treatment with varying doses of ionizing radiation (IR). The expression of DNA checkpoint proteins was analyzed by Western blots and immunohistochemistry. On the basis of the clinical data for the patients, the association between the expression of the components and patients’ survival was investigated. The expression levels of TopBP1 and phosphorylated Chk1 (P-Chk1) protein were higher in radioresistant lung cancer cell lines compared to radiosensitive cell lines. We previously assessed radiation survival of lung cancer cell lines after treating them with Chk1 inhibitor, AZD7762. AZD7762 significantly sensitized both radioresistant and radiosensitive cells to IR. We also observed a strong inverse relationship between progression-free survival (PFS) and expression level of P-Chk1 and TopBP1. This study, which is the first clinical report that connects DNA damage checkpoints and prognosis of brain metastasis, supports these two proteins to be promising targets for overcoming the radioresistance in brain metastasis.

Key words: DNA damage checkpoint; Metastatic brain tumor; Phosphorylated Chk1 (P-Chk1); TopBP1; Radioresistance

1These authors provided equal contribution to this work.
Address correspondence to Do-Hyun Nam, Department of Neurosurgery, Samsung Medical Center and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710, South Korea. Tel: +82-2-3410-3497; Fax: +82-2-3410-0048; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 391–398, 2011
0965-0407/11 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504011X13127606672922
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Role of Peroxiredoxin V in (−)-Epigallocatechin 3-gallate-Induced Multiple Myeloma Cell Death

Lina Ren,* Hee-Young Yang,* Hoon-In Choi,* Kyoung-Jin Chung,* Ung Yang,* Il-Kwon Lee,† Hyeoung-Joon Kim,† Dong-Seok Lee,‡ Byung-Ju Park,* and Tae-Hoon Lee*

*Department of Biochemistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for Dental School, Chonnam National University, Gwangju, South Korea
†Genome Research Center for Hematopoietic Disease, Chonnam National University Hwasun Hospital, Jeonnam, South Korea
‡School of Life Sciences & Biotechnology, College of Natural Sciences, Keungpook National University, Daegu, South Korea

(−)-Epigallocatechin 3-gallate (EGCG) is a potent antioxidant polyphenol in green tea that acts as an anticancer agent via both direct and indirect pathways. Although the relationship between EGCG’s anticancer effects and its antioxidant activity is not fully understood, it is known that EGCG stimulates production of reactive oxygen species (ROS), which induce oxidative stress leading to cell death. In IM9 multiple myeloma cells, EGCG acted in a dose- and time-dependent manner to induce apoptotic cell death. Among the antioxidant enzymes expressed in IM9 cells, levels of peroxiredoxin V (PrdxV) were selectively and significantly reduced by EGCG. Moreover, the ROS scavenger NAC completely inhibited EGCG-induced apoptosis and PrdxV reduction, while overexpression of PrdxV, but not a PrdxVC48S mutant, protected IM9 cells from EGCG-induced apoptosis. EGCG-induced reductions in cell viability and PrdxV levels were also observed in primary CD138+ multiple myeloma cells from patients. These results suggest that PrdxV is a key target via which EGCG mediates its anticancer effects.

Key words: Peroxiredoxin V (PrdxV); (−)-Epigallocatechin 3-gallate (EGCG); Apoptosis; Multiple myeloma cell

Address correspondence to Tae-Hoon Lee, Ph.D., Department of Biochemistry, School of Dentistry, Chonnam National University, 300 Yongbong Dong, Buk-Ku, Gwangju 500-757, South Korea. Tel: +82 62 5304842; Fax: +82 62 5304848; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 399–402, 2011
0965-0407/11 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504011X13123323849753
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Subacute Transient Encephalopathy Induced by Erlotinib

Takako Okyuama, Yuki Akazawa, Junji Uchida, Kazumi Nishino, Toru Kumagai, and Fumio Imamura

Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

Erlotinib (TarcevaÒ) is a selective small-molecule inhibitor of HER1/EGFR tyrosine kinases that is especially effective for treating non-small cell lung cancer (NSCLC) harboring a constitutively active EGFR mutation. Erlotinib treatment frequently induces adverse effects such as skin rashes and diarrhea, but severe toxicity is rare. Whereas interstitial pneumonia induced by erlotinib is sometimes observed, toxicity in the central nerve system (CNS) is rarely reported. Here, we report a 75-year-old female NSCLC patient who developed subacute encephalopathy during erlotinib treatment. She showed increased irritability, loss of consciousness, convulsions, confusion, lethargy, and urinary incontinence. A brain MRI and an analysis of her CSF and blood serum detected no other causes of encephalopathy such as brain metastasis, leptomeningeal carcinomatosis, metabolic disturbances, liver damage, or infectious disease. Her subacute encephalopathy was considered to have been induced by erlotinib because her symptoms improved rapidly and spontaneously after the cessation of erlotinib treatment.

Key words: Chemotherapy; Encephalopathy; Erlotinib; Transient

Address correspondence to Takako Okuyama, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511 Japan. Tel: +81-6-6972-1181; Fax: +81-6-6971-7636; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 403–406, 2011
0965-0407/11 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504011X13123323849799
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Compassionate Use of Everolimus in a Patient With a Neuroendocrine Tumor: A Case Report and Discussion of the Literature

Sara Pusceddu, Massimo Milione, and Giuseppe Procopio

Fondazione IRCCS Istituto Nazionale dei Tumori of Milan, Milan, Italy

Neuroendocrine tumors (NETs) represent a relatively rare form of neoplasias for which, in advanced unresectable stages, palliative treatment options remain limited largely to the use of somatostatin analogues or chemotherapy. Several newer targeted therapeutic options, alone or in combination with somatostatin analogues, are currently undergoing clinical evaluation for the treatment of NETs. This article reports the compassionate use of everolimus in combination with long-acting octreotide, in a 58-year old Italian female patient with a well-differentiated neuroendocrine gastric tumor who, since October 2004, has failed multiple previous therapies. Starting in October 2008, the patient has received intramuscular octreotide LAR 30 mg every 28 days plus everolimus 10 mg/day. The patient has reported benefits of symptoms (reduction of pain severity), objective response [improvement of liver function (reductions in LDH, ALP and total bilirubin) and chromogranin A], and radiological response (reduction in target lesions on CT). The patient has experienced an improved quality of life, increased life expectancy, and remains on this well-tolerated treatment regimen.

Key words: Compassionate use; Everolimus; Neuroendocrine tumor; Octreotide; Targeted therapies

Address correspondence to Giuseppe Procopio, Fondazione Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milan; Italy. Tel: +39-02-23902557; Fax: +39-02-23902149; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 407–443, 2011
0965-0407/11 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096504011X13127606672832
E-ISSN 1555-3906
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved


Review

A Novel Prosurvival Model for Cancer Under Environmental Challenge: The “Heart-Felt” Message for Therapeutic Intervention

John A. Loudon

Wetherill Park Medical Centre, Sydney, Australia

In the present review I propose a novel model system to analyze and to aid prediction of suitable targeted treatments aimed at therapy-resistant cancer cells. The concept of cancer cell prosurvival reaction to adverse external tumor microenvironment is explored in the context of the reaction of myocardium to unfavorable physiologic conditions. Many of the protective and indeed nonprotective (tumor suppressor) reactive mechanisms in both cancer and heart tissue challenged with an adverse environment follow similar and predictable patterns. Based on these observations, a model is constructed that may aid prediction of future therapies aimed to target cancer—particularly chemotherapy/radiotherapy resistance and dormant disease. As another feature of the model, ways to better forecast future therapies aimed at augmenting cardioprotective paths is made possible through understanding of pathways used to sustain cancer cells under external challenges.

Key words: Ischemic myocardium; Cardiac pre-/postconditioning; Hibernating myocardium; Dormant cancer; Chemotherapy/radiotherapy resistance; Prosurvival factors

Address correspondence to John A. Loudon, Ph.D., BDS(Hons) Syd; Cert Oral Path. FAAOMP (Ohio), at his current address: Wetherill Park Medical Centre, Suite 101, Stockland Mall, Wetherill Park, Sydney, NSW, 2164, Australia. Tel: +61-2-9756-3636; Fax: +61-2-9756-3637; Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it