Oncology (ONCOLOGY-BASEL)

Publications in this journal

• Article: Trastuzumab combined with pegylated liposomal doxorubicin in patients with metastatic breast cancer : phase II study of the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation

  Christos Christodoulou, Ioannis Kostopoulos, Haralabos Kalofonos, Evangelos Lianos, Mattheos Bobos, Evangelos Briasoulis, Helen Gogas, Evangelia Razis, Dimosthenis Skarlos, George Fountzilas
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  ABSTRACT: Combination of trastuzumab and anthracyclines in metastatic breast cancer (MBC) is precluded due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is the least cardiotoxic among the anthracyclines. We performed a phase II study of trastuzumab and PLD with biomarker evaluation. Methods: Patients with MBC and HER2 overexpression, assessed as 3+ at local laboratories, received trastuzumab 8 mg/kg as loading dose followed by 6 mg/kg in combination with PLD 30 mg/m2, both given every 3 weeks. To be eligible, patients should have received first-line chemotherapy for MBC or should have relapsed within a year of adjuvant taxane. Tumor tissue blocks were collected for central review and exploratory biomarker evaluation. Left-ventricular ejection fraction (LVEF) was closely monitored by cardiac ultrasound. Results: Among 37 patients, an overall response rate of 22% was observed with a progression-free survival (PFS) of 6.5 months (0.8–31.1, 95% CI 2.7–10.3) and a survival of 18.7 months (1.6–40.8, 95% CI 3.7–33.7). No decline in LVEF was noticed. Overexpression of mTOR and TOP2A gene alterations were associated with better PFS. PTEN gene deletion was associated with resistance to treatment. Conclusion: Trastuzumab combined with PLD every 3 weeks is feasible, effective and safe in HER2-positive patients.
  Oncology 01/2013;
• Article: MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer.

  Chattopadhyay S, Machado-Pinilla R, Manguan-García C, Belda-Iniesta C, Moratilla C, Cejas P, Fresno-Vara JA, de Castro-Carpeño J, Casado E, Nistal M, Gonzalez-Barón M, Perona R
  Oncology 06/2006; 25(23):3335.
• Article: Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer.

  Cristian Massacesi, Annalisa La Cesa, Fabiana Marcucci, Alberta Pilone, Marco B L Rocchi, Laura Zepponi, Daniele Santini, Giuseppe Tonini, Luciano Burattini
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  ABSTRACT: Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m(2) on day 1, and capecitabine (Xeloda) 2,000 mg/m(2)/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with >/=3 chemotherapy lines. A median of 6 cycles were given (range 1-19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0-50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer.
  Oncology 02/2006; 70(4):294-300.
• Article: Should men with serum prostate-specific antigen < or =4 ng/ml and normal digital rectal examination undergo a prostate biopsy? A literature review.

  Pietro Pepe, Paolo Panella, Letterio D'Arrigo, Francesco Savoca, Michele Pennisi, Francesco Aragona
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  ABSTRACT: The clinical significance of a prostate cancer (PCa) cannot be determined solely by tumor volume (< or =0.5 cm(3)), as small tumors of higher Gleason grade and tumors occurring in younger men may become clinically significant even though the initial volume at diagnosis is small. A certain number of these minimal cancers are likely to remain clinically insignificant; however, it is unpredictable how many can progress beyond the curable stage by the time there is a rise in serum prostate-specific antigen (PSA) values. Compared to clinically detected PCa, PCa detected exclusively by PSA screening (clinical stage T1c) are less likely to be advanced but no more likely to be insignificant in terms of volume, pathologic stage, and Gleason pattern. Only 10-15% of PSA-detected cancers have the features of PCa found at autopsy or in cystoprostatectomy specimens. Actually, 25-30% of PCa are detected with PSA values between 2.5 and 4 ng/ml, and most of these cancers are clinically significant. Evidence from both retrospective and longitudinal studies has shown that the risk of a PCa is dependent on the patient's age and the initial serum PSA. This allows an individualized approach to PCa screening programs, and PSA cutoff values for biopsy indication may be lowered in selected patients.
  Oncology 02/2006; 70(2):81-9.
• Article: Presentations of phase 2 clinical trial abstracts at a national oncology meeting: potential implications for subsequent publication in the peer-reviewed literature.

  Maurie Markman
  Oncology 02/2006; 71(1-2):146-7.
• Article: Plausible linkage of hypoxia-inducible factor (HIF) in uterine endometrial cancers.

  Jiro Fujimoto, Eriko Sato, Syed Mahfuzul Alam, Israt Jahan, Hiroshi Toyoki, Bao Li Hong, Hideki Sakaguchi, Teruhiko Tamaya
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  ABSTRACT: Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with the angiogenic transcription factor hypoxia-inducible factor (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine endometrial cancers. Sixty patients underwent curative resection for uterine endometrial cancers. In the tissue of 60 uterine endometrial cancers, HIF-1alpha, HIF-2alpha and HIF-1beta mRNA levels, and the ratio of angiopoietin (Ang)-2 to Ang-1 (Ang-2/Ang-1) mRNA levels were determined by RT real-time PCR; histochemical scores and localization of HIF-1alpha were determined by immunohistochemistry. Levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and interleukin-8 (IL-8) were determined by enzyme immunoassay. In stage I uterine endometrial cancers, HIF-1alpha histochemical scores and mRNA levels significantly increased with myometrial invasion of uterine endometrial cancers. HIF-1alpha histochemical scores and mRNA levels correlated with the levels of Ang-2/Ang-1 and IL-8. The angiogenic mediator HIF-1alpha, linked to Angs and IL-8, might work on angiogenesis with myometrial invasion of cancer cells in uterine endometrial cancers.
  Oncology 02/2006; 71(1-2):95-101.
• Article: Frequent occurrence of abnormal E-cadherin/beta-catenin protein expression in advanced gallbladder cancers and its association with decreased apoptosis.

  Kenro Hirata, Tetsuo Ajiki, Taro Okazaki, Hideki Horiuchi, Tsunenori Fujita, Yoshikazu Kuroda
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  ABSTRACT: Our aim is to assess the clinicopathological significance of E-cadherin and beta-catenin expression, as well as their association with apoptosis in gallbladder cancers. The expression of E-cadherin and beta-catenin proteins was examined in 4 biliary tract cancer cell lines and 49 gallbladder cancer specimens by immunofluorescent or immunohistochemical methods and Western blotting. The apoptotic status was evaluated in the cell lines by poly(ADP-ribose) polymerase Western blotting and in the tumors by the TdT-mediated dUTP nick end labeling assay. Expression of poly(ADP-ribose) polymerase (apoptosis) was only seen in cell lines that expressed both E-cadherin and beta-catenin. Reduced expression of E-cadherin and beta-catenin was frequently seen in advanced gallbladder cancer cases (61 and 83%, respectively) relative to pT1 cases (25 and 63%, respectively). The 5-year survival rate in cases with reduced E-cadherin expression was 26%, significantly lower than in cases with preserved E-cadherin expression (70%; p = 0.017). Cases with reduced expression of both had lower apoptotic indices and showed a worse prognosis compared with cases with reduced expression of either E-cadherin or beta-catenin (p = 0.04 and 0.049, respectively). The expression of E-cadherin or beta-catenin frequently diminishes as the tumor progresses, and abnormalities of E-cadherin and beta-catenin expression were associated with decreased apoptosis in gallbladder cancers. E-cadherin expression might be a useful prognostic marker in this tumor.
  Oncology 02/2006; 71(1-2):102-10.
• Article: Efficacy and tolerability of capecitabine with weekly paclitaxel for patients with metastatic breast cancer: a phase II report of the SAKK.

  Ute Gick, Christoph Rochlitz, Walter Mingrone, Bernhard Pestalozzi, Daniel Rauch, Pierluigi Ballabeni, Doris Lanz, Viviane Hess, Stefan Aebi
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  ABSTRACT: Paclitaxel and capecitabine have proven activity in the treatment of metastatic breast cancer (MBC). Paclitaxel increases the expression of thymidine phosphorylase, the enzyme that activates capecitabine. The purpose of this study was to evaluate the efficacy and tolerability of capecitabine in combination with weekly paclitaxel largely as first-line therapy in patients with MBC. From April 2002 to September 2004, 19 patients with MBC received oral capecitabine (1,000 mg/m(2) twice daily on days 1-14) plus i.v. paclitaxel (80 mg/m(2) on days 1, 8 and 15) in a 21-day cycle for a maximum of 6 cycles. After a median follow-up of 19.3 months the overall response rate was 63% with 1 complete response (5%) and 11 partial responses (58%). Disease was stabilized in 1 patient (5%) and 3 patients had progressive disease (16%). Three patients were unable to be assessed for response to treatment. Median time to progression was 3.3 months, median time to treatment failure 3.0 months and median overall survival 13.8 months. A substantial number of patients experienced major side effects. The most common treatment-related adverse events were hand-foot syndrome (53%; grade 3: 37%), alopecia (42%; grade 3: 26%), diarrhea (32%; grade 3: 11%) and neurotoxicity (32%; grade 3: 16%). Hematologic toxicities were uncommon. The combination of capecitabine and paclitaxel appears to be active in MBC but the safety profile with the dosages used in this trial was unacceptably high and led to a short time to treatment failure. However, based on the efficacy data alternative schedules deserve further evaluation.
  Oncology 02/2006; 71(1-2):54-60.
• Article: PET scans for decision-making in metastatic renal cell carcinoma: a single-institution evaluation.

  M S Dilhuydy, A Durieux, A Pariente, H de Clermont, G Pasticier, J Monteil, A Ravaud
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  ABSTRACT: Therapeutic decision-making in metastatic renal cell carcinoma (MRCC) is based on conventional radiological evaluation. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans may modify this strategy. Patients with MRCC for whom a therapeutic decision had been made underwent an FDG-PET scan in order to complete the standard radiological evaluation. Twenty-four patients and 26 FDG-PET scans were eligible. In 18 patients, metastatic disease was evaluable on the computed tomography (CT) scan; the FDG-PET scan was positive in 16 patients and negative in 10. In 2 patients, the FDG-PET scan was positive while they were considered disease free on radiological evaluation. In 5 patients (20.8%), the previous therapeutic decision was changed. Thirteen patients had a pathological evaluation for 19 sites. One patient out of 13 had a false-positive FDG-PET scan, while 4 sites out of 6 were false-negative. The sensitivity was 75% (95% CI: 47.6-92.7) and the predictive positive value was 92.3% (95% CI: 64-99.8). With a median follow-up of 24 months, 3 patients developed new metastatic sites. Our data suggest that, when positive, an FDG-PET scan may modify the decision made; when negative, it should not modify decision-making especially for surgery, owing to its sensitivity.
  Oncology 02/2006; 70(5):339-44.
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  Article: Combination of multiple mRNA markers (PTTG1, Survivin, UbcH10 and TK1) in the diagnosis of Taiwanese patients with breast cancer by membrane array.

  Chung-Chi Chen, Tsai-Wang Chang, Fang-Ming Chen, Ming-Feng Hou, Sung-Yu Hung, Inn-Wen Chong, Su-Chen Lee, Tian-Hong Zhou, Shiu-Ru Lin
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  ABSTRACT: Early detection is a prerequisite to the effective reduction of morbidity and mortality from breast cancer. The present study intended to employ a high-throughput membrane array to detect a panel of mRNA markers expressed by circulating tumor cells (CTCs) in the peripheral blood of female patients with breast cancer. Peripheral blood was sampled from 92 breast cancer patients and 100 normal persons. CTCs were detected by using a membrane array technique. The markers used included the pituitary tumor transforming gene 1, survivin, UbcH10 and thymidine kinase 1. RESULTs: The results showed that the membrane array could positively detect 5 cancer cells per 1 ml of peripheral blood in breast cancer cell dilution experiments. For the panel of 4 mRNA markers, sensitivity and specificity were elevated up to 86 and 88%, respectively. Furthermore, it was found that the patients' clinicopathological characteristics tumor size (p = 0.006), histologic grade (p = 0.012), lymph node metastasis (p = 0.001) and TNM stage (p = 0.006) significantly correlated with the positive detection rate of the multimarker panel. These findings demonstrated that our multimarker membrane array method could detect CTCs in the circulation of breast cancer patients with considerably high sensitivity and specificity.
  Oncology 02/2006; 70(6):438-46.
• Article: Overexpression of the orotate phosphoribosyl-transferase gene enhances the effect of 5-fluorouracil on gastric cancer cell lines.

  Jyunnya Taomoto, Kazuhiro Yoshida, Yoshiyuki Wada, Kazuaki Tanabe, Kazuo Konishi, Hidetoshi Tahara, Masakazu Fukushima
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  ABSTRACT: Orotate phosphoribosyl-transferase (OPRT) is the initial enzyme of the 5-fluorouracil (5-FU) metabolic pathway, converting 5-FU into 5-fluorouridinemonophosphate, which is the most important mechanism of 5-FU activation. We therefore investigated whether overexpression of the OPRT gene enhances sensitivity to 5-FU. An expression vector of the OPRT gene (pTARGET-OPRT) was transfected into two gastric cancer cell lines, TMK-1 and MKN-45, with low baseline expression levels of OPRT. The sensitivity to and anti-tumor activity of 5-FU were then investigated in vitro and in vivo in these two transfected clones (TMK-OPRT and MKN-OPRT). Although cell growth was unaltered compared to parent cells, overexpression of the OPRT gene was confirmed by Western blotting in both the TMK-OPRT and MKN-OPRT cells. OPRT enzyme activity increased 38-fold in TMK-OPRT cells and 8.0 fold in MKN-OPRT cells compared to their parent cells. Interestingly, although the sensitivity to Adriamycin, cis-platinum, mitomycin C and paclitaxel was unaltered in the transfected clones, the sensitivity to 5-FU was increased 14.2- and 6.0-fold in TMK-OPRT and MKN-OPRT cells, respectively, compared to their parent cells. Moreover, enhanced sensitivity was also confirmed in the in vivo study. The results indicate that overexpression of the OPRT gene plays an important role in the antiproliferative effect of 5-FU and might therefore be a predictive factor of response to 5-FU in gastric cancer patients.
  Oncology 02/2006; 70(6):458-64.
• Article: Quality of life in patients with oesophageal and gastric cancer: an overview.

  Thierry Conroy, Frédéric Marchal, Jane M Blazeby
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  ABSTRACT: An accurate assessment of health-related quality of life (QoL) in patients with oesophageal or gastric cancer (OGC) is essential to inform clinical decisions by providing insights into patients' experiences of the impact of the disease and its treatments on physical, social and emotional health. Robust QoL questionnaires have been developed and validated in the past decade to measure the QoL of OGC patients. Baseline QoL variables are also prognostic for survival in patients with oesophageal cancer or metastatic gastric cancer. This article reviews the impact of surgery and reconstructive techniques, as well as of adjuvant and palliative treatments on the QoL of patients with OGC.
  Oncology 02/2006; 70(6):391-402.
• Article: Single-agent gemcitabine for biliary tract cancers. Study outcomes and systematic review of the literature.

  Takayoshi Kiba, Tsutomu Nishimura, Shigemi Matsumoto, Etsuro Hatano, Akira Mori, Shujiro Yasumi, Ryuichiro Doi, Iwao Ikai, Toshiyuki Kitano, Takafumi Nishimura, Kiyotsugu Yoshikawa, Hiroshi Ishiguro, Kazuhiro Yanagihara, Emiko Doi, Satoshi Teramukai, Masanori Fukushima
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  ABSTRACT: The aim of this study was to investigate the outcomes of gemcitabine-treated patients with inoperable biliary tract cancers. We conducted a retrospective study of consecutively treated 22 inoperable biliary tract cancer patients with gemcitabine (500-1,000 mg/m(2) on days 1, 8, 15 every 4 weeks) as first-line, and 17 patients as second- or third-line treatment. The response rate of patients treated with gemcitabine as first-line and second- or third-line treatment was 5.3 and 28.5%, respectively. The median overall survival time in the first-, and second- or third-line treatment groups was 8.3 and 17.0 months, and the 1-year survival rate was 44.0 and 50.9%, respectively. The present study also suggests the possibility that the prognosis of patients with high levels of C-reactive protein and total bilirubin, or a low level of albumin might be worse. Our results indicate that the treatment of inoperable biliary tract cancers with gemcitabine is feasible. There was no difference in the response rate and overall survival between biliary tract cancer patients in the first- and second- or third-line treatment groups. We also present the systematic review of literature of the recent treatment results of biliary tract cancers treated with gemcitabine.
  Oncology 02/2006; 70(5):358-65.
• Article: Randomised trial comparing three different schedules of infusional 5FU and raltitrexed alone as first-line therapy in metastatic colorectal cancer. Final results of the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 trial.

  M Ducreux, O Bouche, J P Pignon, M Mousseau, J L Raoul, P Cassan, B Leduc, C Berger, A Dunant, J Fournet, L Bedenne
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  ABSTRACT: LV5FU2 with high-dose leucovorin (LV), weekly infusional 5-fluorouracil (5FU) (AIO schedule) and raltitrexed have been demonstrated to be active agents in first-line treatment of colorectal cancer. We performed a 4-arm randomised trial to compare (1) a low-dose intravenous bolus of LV (20 mg/m2), followed by an intravenous bolus of 5FU (400 mg/m2), followed by a 22-hour continuous infusion of 5FU (600 mg/m2) on day 1 and day 2/2 weeks (ldLV5FU2 arm), (2) a weekly continuous infusion of high-dose 5FU (2.6 g/m2/week) for 6 weeks followed by a rest week (HD-FU arm) and (3) raltitrexed (Tomudex arm; 3 mg/m2/3 weeks) to standard LV5FU2. From 1997 to 2001, 294 patients were included. The 4 arms were well balanced for sex ratio, age, WHO performance status, the primary tumour site and prior adjuvant chemotherapy. Treatment was stopped due to low accrual. Two toxicity-related deaths were observed in the Tomudex arm. The treatments gave rise to different rates of grade 3-4 neutropenia (3, 4, 11 and 14% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively, p = 0.028), leucopenia and vomiting. At least one episode of grade 3-4 toxicity was observed in 27, 25, 38 and 47% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.016). An objective response was observed in 28, 21, 22 and 10% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.04). Progression-free survival (PFS) of the patients in the Tomudex arm was statistically lower compared to that of patients treated with LV5FU2 or ldLV5FU2 (combined group; p = 0.013, log rank test). In conclusion, Tomudex is more toxic and yields shorter PFS than infusional 5FU. Despite the early closure of the study and the lack of power of the comparison, it seems that ldLV5FU2 could be considered as an active, easier and less expensive option for the treatment of metastatic colorectal cancer compared to classic LV5FU2 or weekly HD-FU.
  Oncology 02/2006; 70(3):222-30.
• Article: Psychometric evaluation of the Brief Cancer Impact Assessment among breast cancer survivors.

  Catherine M Alfano, Bonnie A McGregor, Alan Kuniyuki, Bryce B Reeve, Deborah J Bowen, Ashley Wilder Smith, Kathy B Baumgartner, Leslie Bernstein, Rachel Ballard-Barbash, Kathleen E Malone, Patricia A Ganz, Anne McTiernan
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  ABSTRACT: The increasing number of cancer survivors brings greater attention to the biopsychosocial impact of surviving cancer. Instruments exist that measure quality of life (QOL), symptoms, and specific types of functioning after cancer; however, a reliable and valid assessment of the perceived impact of cancer (IOC) on the life plans and activities of cancer survivors has been missing. This study evaluated the psychometric properties of the 16-item Brief Cancer Impact Assessment (BCIA). Factor analysis with Promax oblique rotation established the factor structure of the BCIA in 783 ethnically diverse breast cancer survivors, >or=2 years after diagnosis. Construct validity was assessed by comparing factor-based scale means by demographic and treatment characteristics, and correlating scales with psychosocial and health-related QOL scales. Factor analysis revealed four factors measuring the IOC on caregiving and finances, exercise and diet behaviors, social and emotional functioning, and religiosity. Scale scores differed by demographic and treatment characteristics according to expectations, and the pattern of correlations with psychosocial and health-related QOL generally supported the construct validity of the scales. Including the BCIA with measures of QOL, symptoms, and functioning will allow researchers to gain a more comprehensive assessment of the biopsychosocial IOC in survivors.
  Oncology 02/2006; 70(3):190-202.
• Article: Defective expression of HRK is associated with promoter methylation in primary central nervous system lymphomas.

  Mitsutoshi Nakamura, Eiwa Ishida, Keiji Shimada, Hiroyuki Nakase, Toshisuke Sakaki, Noboru Konishi
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  ABSTRACT: Recently, it has been reported that expression of the HRK gene was significantly reduced by hypermethylation in astrocytic tumors. Our aim is to verify the alterations in the HRK gene in primary central nervous system lymphomas (PCNSLs). We analyzed the hypermethylation status and expression of the gene and 12q13.1 loss of heterozygosity in 31 PCNSLs. A total of 13 PCNSLs (31%) demonstrated hypermethylation in either the promoter or exon 1; loss of HRK expression was immunohistochemically observed in 9 tumors and was significantly associated with promoter methylation. In addition, higher apoptotic counts were associated with HRK positivity. PCNSLs with HRK methylation also showed methylation of multiple genes, such as p14ARF, p16INK4a, RB1, p27Kip1 and O6-MGMT. Patients with tumors demonstrating concurrent methylation of more than half of their genes demonstrated significantly poorer survival and earlier recurrence. Hypermethylation of the HRK promoter alone was not associated with overall outcome, but relapse-free survival was significantly shorter. Our findings suggest that transcriptional repression of HRK is caused by promoter hypermethylation in PCNSL, and that the loss of HRK associated with the methylation profile of other genes is a potential step in the modulation of cellular death by apoptosis during PCNSL tumorigenesis.
  Oncology 02/2006; 70(3):212-21.
• Article: A newly identified MAGE-3-derived, HLA-A24-restricted peptide is naturally processed and presented as a CTL epitope on MAGE-3-expressing gastrointestinal cancer cells.

  Naoto Miyagawa, Koji Kono, Kousaku Mimura, Hideo Omata, Hidemitsu Sugai, Hideki Fujii
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  ABSTRACT: In order to broaden the possibility for anti-MAGE-3 immune targeting, it is important to identify HLA-A24-restricted epitopes derived from MAGE-3, since HLA-A24 is one of the most common alleles in Japanese and Asian people. In the present study, we defined a new MAGE-3 derived, HLA-A24-binding peptide presented as a CTL epitope on gastrointestinal cancer cells. A panel of MAGE-3-derived peptides (9mer and 10mer) with the HLA-A24-binding motif was selected, and identification of MAGE-3-derived, HLA-A24-restricted CTL epitopes was performed by a reverse immunology approach. To induce MAGE-3-peptide specific CTLs, PBMCs were repeatedly stimulated with monocyte-derived, mature DCs pulsed with the peptides. Subsequent peptide-induced T cells were tested for their specificities by ELISPOT, tetramer and cytotoxic assay. CTL clones were then obtained from the CTL line by limiting dilution. The peptide-inducing CTLs revealed that MAGE-3(113)-peptide was reacted as a CTL epitope in a HLA-A24-restricted fashion, confirmed by ELISPOT and cytotoxic assays. In addition, the MAGE-3(113)-specific CTL clones, confirmed by tetramer assay, showed that the MAGE-3(113) epitope is naturally processed and presented as the CTL epitope on MAGE-3-expressing gastrointestinal cancer cells by evaluating the cold target inhibition assays. The newly identified MAGE-3(113)-peptide epitope is naturally processed and presented as the CTL epitope on MAGE-3-expressing gastrointestinal cancer cells, indicating that anti-MAGE-3 immune targeting with the MAGE-3(113) peptide is a promising approach for treatment.
  Oncology 02/2006; 70(1):54-62.
• Article: Expression of polo-like kinase 1 (PLK1) protein predicts the survival of patients with gastric carcinoma.

  Shingo Kanaji, Hiroaki Saito, Shunichi Tsujitani, Sachiko Matsumoto, Shigeru Tatebe, Akira Kondo, Mitsuhiko Ozaki, Hisao Ito, Masahide Ikeguchi
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  ABSTRACT: To assess the prognostic value of polo-like kinase 1 (PLK1), an important regulator of cell cycle progression, in patients with gastric carcinoma. PLK1 expression was determined in 160 gastric carcinoma patients by immunohistochemistry and compared with p53 expression and the proliferating cell nuclear antigen-labeling index (PCNA-LI) to evaluate the effect of PLK1 on tumor progression. Furthermore, PLK mRNA expression was determined in 26 advanced gastric cancer patients by reverse transcription-polymerase chain reaction (RT-PCR). PLK mRNA expression was detected in 25 (96.2%) patients by RT-PCR. Immunohistochemical staining revealed PLK1 expression in 84 (52.5%) patients. There were no significant relationships between PLK1 expression and various clinicopathological factors. PLK1 expression was significantly correlated with the PCNA-LI, but not p53 expression. The prognosis of patients with PLK1-positive tumors was significantly worse than that of patients with PLK1-negative tumors (p < 0.05). Moreover, multivariate analysis revealed that PLK1 expression was an independent prognostic factor. Patients with PLK1-positive and high PCNA-LI tumors showed a significantly poorer prognosis than patients with PLK1-negative and/or low PCNA-LI tumors. Furthermore, the prognosis of patients with PLK1- and p53-positive tumors was significantly worse than that of patients with PLK1- and p53-negative or PLK1-negative and p53-positive tumors. PLK1 expression may be a critical indicator of a poor prognosis in patients with gastric carcinoma.
  Oncology 02/2006; 70(2):126-33.