|ognizant Communication Corporation|
AN INTERNATIONAL JOURNAL
INCORPORATING ANTI-CANCER DRUG DESIGN
VOLUME 16, NUMBER 6
Oncology Research, Vol. 16, pp. 251-260
0965-0407/07 $90.00 + .00
Copyright © 2007 Cognizant Comm. Corp.
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Ineffectiveness of American Ginseng in the Prevention of Dimethylbenzanthracene-Induced Mammary Tumors in Mice
Gregory T. Wurz, Cristina Marchisano-Karpman, and Michael W. DeGregorio
Department of Internal Medicine, Division of Hematology and Oncology, Cancer Center, The University of California, Davis, Sacramento, CA 95817, USA
The potential of American ginseng (AG) (Panax quinquefolium), a commonly used herbal remedy believed to have anticarcinogenic effects, to prevent the development of mammary tumors was evaluated in a mouse model of dimethylbenzanthracene (DMBA)-induced mammary carcinoma. Ginsenosides, believed to be the active components of ginseng and that have a chemical structure similar to estradiol, have previously been shown to possess phytoestrogen-like qualities similar to the soy isoflavone genistein. The effects of AG, administered as powdered root, were compared to the selective estrogen receptor modulators tamoxifen and ospemifene. Eighty-three female SENCAR mice were divided into four treatment groups: control (N = 23), AG (N = 20), ospemifene (N = 20), and tamoxifen (N = 20). American ginseng, ospemifene, and tamoxifen were administered at a dose of 50 mg/kg/day orally by gavage, with the control mice receiving vehicle only. For the first 6 weeks, all mice received 20 mg/day DMBA in combination with their respective treatments. DMBA was then withdrawn, and daily treatments continued for a total of approximately 52 weeks. As expected, ospemifene (p = 0.01) and tamoxifen (p = 0.004) significantly reduced the incidence of mammary tumors compared to the control mice, which had a mammary tumor incidence of approximately 57%. The incidence of mammary carcinomas in the AG group was 40%, a reduction of approximately 29% compared to control. These results suggest that AG may still have the potential to prevent the development of mammary tumors in a chemically induced breast cancer mouse model, although the present study showed no significant difference between control and AG-treated mice.
Key words: Breast cancer; Dimethylbenzanthracene (DMBA); American ginseng; Ospemifene; Selective estrogen receptor modulator (SERM); Tamoxifen
Address correspondence to Dr. Michael W. DeGregorio, Professor, Department of Internal Medicine, Division of Hematology and Oncology, Cancer Center, The University of California, Davis, 4501 X Street Suite 3016, Sacramento, CA 95817, USA. Tel: 916-734-2360; Fax: 916-734-2374; E-mail: firstname.lastname@example.org
Genetic and Epigenetic Alterations of LTF at 3p21.3 in Nasopharyngeal Carcinoma
Hong-Mei Yi,1,2 Hui Li,1 Dan Peng,1 He-Jun Zhang,1 Lei Wang,1 Ming Zhao,1 Kai-Tai Yao,1 and Cai-Ping Ren1
1Cancer Research Institute, Xiang-Ya School of Medicine,
Central South University, Changsha, Hunan 410078, P. R. China
2Institute of Clinical Medicine, Hunan Province People's Hospital, Changsha, Hunan 410005, P. R. China
To investigate the roles of lactotransferrin gene (LTF, also referred to as the lactoferrin gene, LF), located at 3p21.3 within the common minimal deletion region, in the pathogenesis of nasopharyngeal carcinoma (NPC), we first detected its expression level in 33 primary NPC tissues and 15 chronic nasopharyngitis tissues. Absent expression or downregulation of LTF were observed in 76% (25 of 33) of primary NPC tissues. We further found that 25% (5 of 20) of NPC specimens had loss of heterozygosity (LOH) at the LTF locus. LTF mutation assessed by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing was noted in 30% (6 of 20) of primary NPC tissues. In addition, hypermethylation of LTF promoter region was found in 63.6% (21 of 33) of primary NPC samples but not in chronic nasopharyngitis tissues. The LTF transcripts in NPC cell lines increased upon treatment with the demethylation compound, 5-aza-2-deoxycytidine. In conclusion, our data indicate that two-hit silencing of LTF through genetic and epigenetic changes may be a common and important event in the carcinogenesis of NPC.
Key words: Nasopharyngeal carcinoma; Lactotransferrin; Loss of heterozygosity (LOH); Mutation; Methylation
Address correspondence to Cai-Ping Ren, M.D., Cancer Research Institute, Xiang-Ya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, P. R. China. Tel: 86-731-2355066; Fax: 86-731-4360094; E-mail: email@example.com
The Expression of Bcl-2 Family Proteins and Spontaneous Apoptosis in Laryngeal Carcinomas
George G. Chen, Alexander C. Vlantis, Ernest C. W. Chak, Han Ching Liu, Michael C. F. Tong, and Charles A. van Hasselt
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
Bcl-2 family proteins play an important role in the growth and biological behavior of tumors. This study aimed to determine Bcl-2 family proteins in laryngeal carcinoma and to examine their relationship with spontaneous apoptosis. The material studied was from 39 patients with laryngeal carcinoma. It was found that the expression of both Bak and Bax was lower in tumor tissues than in nontumor tissues. However, there was no difference in the expression of Bcl-2 between tumor and nontumor tissues. The frequency of spontaneous apoptosis was lower in tumor tissues than in nontumor tissues but was not significantly related to the expression of Bak, Bax, or Bcl-2. Bak was decreased in moderately differentiated tumors compared to well-differentiated tumors. In contrast to Bak, the expression of Bcl-2 was increased in moderately differentiated tumors compared to well-differentiated tumors. These results indicate that the reduction in Bak may be associated with an increase in tumor grade and dedifferentiation in laryngeal carcinomas. The lack of correlation between apoptosis and the expression of Bcl-2 family proteins suggests that spontaneous apoptosis in laryngeal carcinoma is a complex process and that molecules other than Bak, Bax, and Bcl-2 participate in it.
Key words: Laryngeal cancer; Laryngeal carcinoma; Apoptosis; Bak; Bax; Differentiation
Address correspondence to George G. Chen, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. Tel: 852 2632 3934; Fax: 852 2645 0605; E-mail: firstname.lastname@example.org
A Dose Escalation Study of Docetaxel Plus Capecitabine in Combination With Gemcitabine in Patients With Advanced Solid Tumors
K. Amarantidis,1 K. Houhouli,1 K. Papatheodorou,1 A. Miloussis,1 D. Matthaios,1 E. Chatzaki,2 N. Lyrantzopoulos,3 A. Tsaroucha,3 A. Tentes,4 and S. Kakolyris1
1Department of Medical Oncology, Democritus University of
Thrace, University General Hospital of Alexandroupolis, Greece
2Department of Pharmacology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Greece
3Department of Surgery, Democritus University of Thrace, University General Hospital of Alexandroupolis, Greece
4Department of Surgery, General Hospital of Didimotiho, Greece
Capecitabine (CAP), gemcitabine (GEM), and docetaxel (DOC) have shown interesting activity in a wide range of solid tumors. A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of their combination in patients with refractory solid tumors. Eighteen patients were enrolled. The patients' median age was 60 years, 15 were male, and 11 were chemo-naive. DOC was administered on day 1 as an 1-h (IV) infusion at escalating doses ranging from 40 to 50 mg/m2. GEM was administered on day 1 as a 30-min (IV) infusion at a standard dose of 1500 mg/m2. CAP was administered orally on days 1 to 7 at escalating doses ranging from 1750 to 2500 mg/m2 given as two daily divided doses. Treatment was repeated every 2 weeks. Five different dose levels were examined. At dose level V two out of three enrolled patients presented DLTs (one patient grade 4 neutropenia and grade 3 stomatitis and another grade 3 diarrhea), and thus the recommended MTD for future phase II studies are CAP 2250 mg/m2, DOC 50 mg/m2, and GEM 1500 mg/m2. A total of 124 treatment cycles were administered. Toxicity was generally mild. Grade 3/4 neutropenia was observed in eight (7%) treatment cycles and grade 3 thrombocytopenia in one (1%). There was no febrile episode. Grade 2/3 asthenia was observed in six (33%) patients, grade 2/3 diarrhea in four (22%), and grade 2/3 hand–foot syndrome in three (17%). Other toxicities were uncommon. There was no treatment-related death. One (6%) CR, four (25%) PRs, and six (38%) SD were observed among 16 evaluable patients. Responses were seen in patients with breast (one CR), gastric (three PRs), and pancreatic (one PR) cancer. These results demonstrate that CAP, DOC, and GEM can be safely combined at clinically relevant doses and this regimen merits further evaluation.
Key words: Gemcitabine; Docetaxel; Capecitabine; Solid tumors
Address correspondence to Assoc. Professor Stylianos Kakolyris, Department of Medical Oncology, University General Hospital of Alexandroupolis, Dragana 68100, Alexandroupolis, Greece. Tel: 25510-74053; Fax: 25510-74093; E-mail: email@example.com
Expression of NEU3 (Plasma Membrane-Associated Sialidase) in Clear Cell Adenocarcinoma of the Ovary: Its Relationship With T Factor of pTNM Classification
Hiroyuki Nomura,1 Yutaka Tamada,1 Taeko Miyagi,2 Atsushi Suzuki,1 Momoyo Taira,1 Nao Suzuki,1 Nobuyuki Susumu,1 Tatsuro Irimura,3 and Daisuke Aoki1
1Department of Obstetrics and Gynecology, School of Medicine,
Keio University, Tokyo 160-8582, Japan
2Division of Biochemistry, Miyagi Cancer Center Research Institute, Natori, Miyagi 981-1293, Japan
3Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan
Cell surface carbohydrate expression strongly influences the biological characteristics of cancer cells. Especially, it is known that the change of sialic acid expression could be related to the invasive and metastatic potentials of tumors. This study aimed to investigate sialidase expression of ovarian cancer cells and to evaluate the relationship between plasma membrane-associated sialidase (NEU3) expression and various clinicopathological factors in ovarian clear cell adenocarcinoma patients. In 18 cell lines derived from human ovarian cancers (including clear cell, mucinous, and serous adenocarcinoma), sialidase mRNA expression was evaluated by RT-PCR. NEU1 and NEU3 expression levels were found to be elevated in most cell lines while NEU2 and NEU4 expression was rarely elevated. Interestingly, NEU3 expression was detected in all clear cell adenocarcinoma cell lines. In 71 patients with ovarian clear cell adenocarcinoma, treated at Keio University Hospital from February 1983 to February 2002, NEU3 expression was examined by immunohistochemical staining of surgical specimens and clinocopathological factors were reviewed. NEU3 expression was found to be positive in 77.5% of all cases. Furthermore, a high level of NEU3 expression was significantly correlated with T3 factor of pTNM classification on univariate and multivariate analysis. This is the first report to show that NEU3 is expressed in most of ovarian clear cell adenocarcinoma. And our results show that NEU3 expression is correlated with T factor (pTNM classification) in ovarian clear cell adenocarcinoma.
Key words: Ovarian cancer; Clear cell adenocarcinoma; Sialidase; Plasma membrane-associated sialidase; TNM classification; Peritoneal dissemination
Address correspondence to Yutaka Tamada, M.D., Ph.D., Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Tel: 3-3353-1211, ext. 63960; Fax: 3-3226-1667; E-mail: firstname.lastname@example.org