bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta‐[211AT]astatobenzylguanidine: Further evaluation of a potential therapeutic agent
Authors: Vaidyanathan Gunesan , Strickland Donald K. , Zalutsky Michael R. 
Published: February 2007

AbstractMeta‐[211At]astatobenzylguanidine ([211At]MABG) is an astatinated analogue of meta‐iodobenzylguanidine (MIBG) that could be of value for therapeutic applications. The initial goal of this study was to determine whether [211At]MABG is taken up, like MIBG, by a specific uptake‐1 mechanism. Norepinephrine and desipramine (DMI) decreased [211At]MABG uptake in SK‐N‐SH human neuroblastoma cells. This uptake was found to be energy‐dependent: In mice, pre‐treatment with DMI reduced uptake of[211At]MABG at 1 hr post‐injection in the adrenal and in the heart. Tetrabenazine at a dose of 40 mg/kg reduced uptake of [211At]MABG in the mouse heart in vivo (69% of control) whereas up to 100 μM of tetrabenazine did not affect the in vitro uptake of [211At]MABG in SK‐N‐SH cells. In SK‐N‐SH cells, 53% and 38%, respectively, of the initial uptake of [211At]MABG was retained at 4 hr and 6 hr. For no‐carrieradded (n. c.a.) [121I]MIBG these values were similar, 60% and 48%. The ability of SK‐N‐SH cells to incorporate [3H]thymidine was reduced to less than 50% of control values when treated with as little as 3.2 nCi of [211At]MABG. In contrast, no significant reduction in the thymidine uptake was observed, even with 80 nCi of n. c.a. MIBG. © 1994 Wiley‐Liss, Inc.
Potentiation of cytotoxic cancer therapies by TNP‐470 alone and with other anti‐angiogenic agents
Authors: Teicher Beverly A. , Holden Sylvia A. , Ara Gulshan , Sotomayor Enrique Alvarez , Huang Zhen Dong , Chen Ying‐Nan , Brem Harold 
Published: February 2007

AbstractThe ability of TNP‐470, a synthetic analog of fumagillin which has been described as an anti‐angiogenic agent, to potentiate cytotoxic cancer therapies was investigated in vivo in the murine FSaIIC fibrosarcoma and the Lewis lung carcinoma. TNP‐470 was more toxic toward FSaIIC tumor cells from tumors treated in vivo than toward bone‐marrow CFU‐GM from the same animals. TNP‐470 had a dose‐modifying effect on the toxicity of cyclophosphamide toward FSaIIC tumor cells which amounted to an 8‐fold increase in tumor‐cell killing at a cyclophosphamide dose of 500 mg/kg. Treatment with TNP‐470 and minocycline increased the permeability of the FSaII fibrosarcoma in vivo to the fluorescent dye Hoechst 33342 and increased the killing of both the bright and the dim tumor cells by cyclophosphamide. TNP‐470, especially in combination with minocycline, formed a highly effective modulator combination for treatment of the Lewis lung carcinoma with cytotoxic cancer therapies against primary and metastatic disease. The combination of TNP‐470/minocycline and cyclophosphamide led to 40 to 50% long‐term survivors in Lewis‐lung‐carcinoma‐bearing animals. Our results indicate that the use of anti‐angiogenic modulators in cancer therapy is a very promising area for further study. © 1994 Wiley‐Liss, Inc.
DNA repair capacity as a risk factor for non‐melanocytic skin cancer—a molecular epidemiological study
Authors: Hall Janet , English Dallas R. , Artuso Marina , Armstrong Bruce K. , Winter Michael 
Published: February 2007

AbstractCapacity to repair UV‐induced DNA damage was studied by use of a host cell reactivation assay in T lymphocytes isolated from 86 cases and 87 controls (aged 44‐68 years) who were participants in a population‐based case‐control study of basal cell (BCC) or squamous cell (SCC) carcinoma of the skin in Geraldton, Western Australia. Lymphocytes were cultured and transfected with either control or UV‐irradiated plasmids (254 mm, 350 J/m2) containing a reporter gene [the chloramphenicol‐acetyltransferase (CAT) gene], and the repair capacity was determined by measuring CAT gene expression in protein extracts prepared from the transfected cells. DNA repair activity was 1.07 (95% confidence interval 0.94‐1.26) times greater in BCC cases than in controls for each 350 J/m2 increment in UV dose to the plasmids, and 1.04 (95% confidence interval 0.85‐1.26) times greater in SCC cases than in controls, though the differences were not statistically significant. DNA repair activity showed little association with age, sex and viability of the lymphocytes, though it was positively associated with their blastogenic rate (p=0.055).
Risk factors for esophageal cancer in Shanghai, China. II. Role of diet and nutrients
Authors: Gao Yu‐Tang , McLaughlin Joseph K. , Gridley Gloria , Blot William J. , Ji Bu‐Tian , Dai Qi , Fraumeni Joseph F. 
Published: February 2007

AbstractA population‐based case‐control study of esophageal cancer (902 cases, 1,552 controls) in Shanghai, China, investigated the etiologic role of diet. After adjustment for cigarette smoking, alcohol consumption and other risk factors, increasing consumption of fruits, dark orange vegetables and beef or mutton was associated with statistically significant decreasing trends in risk for esophageal cancer. In general, risks were about 40% lower among those in the upper vs. lower quartiles of intake of these foods. Fivefold increases in risk were observed among those who consumed burning hot soup or porridge, with smaller excesses for preserved vegetables, salty and deep fried foods. Nutrient analysis revealed that increased dietary intake of protein, carotene, vitamins C and E and riboflavin was associated with reduced esophageal cancer risk. Our findings support the notion that the reported temporal increases in the per capita consumption of fruits, vegetables and animal products contribute to the substantial reduction in the incidence of esophageal cancer in Shanghai, particularly since cigarette and alcohol use has not decreased.
Human astrocytomas and glioblastomas express monocyte chemoattractant protein‐1 (MCP‐1) in vivo and in vitro
Authors: Desbaillets Isabelle , Tada Mitsuhiro , De Tribolet Nicolas , Diserens Annie‐Claire , Hamou Marie‐France , Van Meir Erwin G. 
Published: February 2007

AbstractExpression of the monocyte chemoattractant protein‐I (MCP‐I) was examined in human central nervous system tumours (glioblastomas and astrocytomas) and normal human brain. Northern blot analysis demonstrated constitutive expression of MCP‐I mRNA in 6 of 12 glioblastoma cell lines. Expression could be stimulated by interleukin (IL)‐Iα and tumour necrosis factor (TNF)‐α in all cell lines tested. Immunoprecipitation demonstrated secretion of both isoforms, MCP‐Iα and ‐β, of the MCP‐I protein. Reverse‐transcription polymerase chain reaction and Northern blot analysis on tissues demonstrated MCP‐I mRNA expression in 17 of 17 glioblastomas, 3 of 6 anaplastic astrocytomas and 6 of 6 low‐grade astrocytomas, as well as in fetal brain but not in normal adult brain. In situ hybridization on 2 glioblastomas and I low‐grade astrocytoma indicates that neoplastic astrocytes and endothelial cells express MCP‐I mRNA in vivo. Moreover, tumour cyst fluids of glioblastomas and astrocytoms were able to induce monocyte chemoattraction in an in vitro assay. This chemotatic activity was specifically neutralized by anti‐MCP‐I antibodies in 9 of samples, further demonstrating the production of bioactive MCP‐I in vivo and supporting an important role for this factor in the infiltration of monocytes/macrophages into tumour tissue.
Lymphotoxin‐α/β heterodimer is expressed on leukemic hairy cells and activated human B lymphocytes
Authors: Mapara Markus Y. , Bargou Ralf C. , Beck Christian , Heilig Benhard , Dörken Bernd , Moldenhauer Gerhard 
Published: February 2007

AbstractThe expression of human lymphotoxin (LT) α/β cell‐surface complex was studied in human B‐cell lines as well as in normal and neoplastic human B lymphocytes. In the absence of TNF receptors, only the human hairy‐cell leukemia (HCL)‐derived cell line JOK‐I revealed constitutive cell‐surface expression of LT but not TNF‐a. Immunoprecipitation experiments with anti‐LT monoclonal antibody (MAb) 9B9 from cell‐surface radioiodinated JOK‐I cells revealed that a cell‐surface lymphotoxin molecule (25 kDa) is expressed in association with a 33‐kDa molecule. Enzymatic digestion with F/N‐glycosidase and O‐glyeosidase showed that both proteins contained N‐linked carbohydrate residues, whereas only the 25‐kDa molecule contained O‐linked sugar residues. Analysis of mRNA expression revealed specific transcripts of LT‐α and LT‐β in JOK‐I cells. Resting tonsillar B cells did not express cell‐surface LT. However, LT‐β mRNA was observable in unstimulated tonsillar B cells, whereas LT‐α mRNA, cell‐surface LT and LT secretion could only be detected upon in vitro activation. Thus LT‐β and α appear to be sequentially expressed in human B cells. Neoplastic B cells from chronic lymphocytic leukemia (BCLL), being devoid of constitutive cell‐surface LT expression, could be induced to express surface LT by in vitro stimulation with Staphylococcux aureus Cowan I (SAC). Constitutive LT‐β transcripts, however, could also be detected in 4 out of 5 cases of BCLL. In contrast, human HCL cells displayed constitutive cell expression of lymphotoxin‐α and β. These findings demonstrate that cell‐surface LT‐α is expressed in association with LT‐β on activated normal B cells and neoplastic B cells representing an activated state.
Hypoxia‐induced resistance to doxorubicin and methotrexate in human melanoma cell lines in vitro
Authors: Sanna Kirsten , Rofstad Einar K. 
Published: February 2007

AbstractRodent cell lines can develop resistance to doxorubicin and methotrexate during hypoxic stress. This has so far not been observed in human tumor cell lines. The purpose of our communication is to show that doxorubicin and methotrexate resistance can also develop in human melanoma cells during exposure to hypoxia. Four cell lines (BEX‐c, COX‐c, SAX‐c, WIX‐c) have been studied. Cells were exposed to hypoxia (O2 concentration < 10 ppm) for 24 hr prior to reoxygenation. Doxorubicin and methotrexate cell survival curves were determined immediately after as well as 18 and 42 hr after reoxygeation. The 4 cell lines were relatively sensitive to doxorubicin without hypoxia pre‐treatment, and all developed resistance during exposure to hypoxia. Hypoxic stress also induced methotrexate resistance in BEX‐c and SAX‐c but not in COX‐c and WIX‐c. BEX‐c and SAX‐c were sensitive to methotrexate without hypoxia pre‐treatment, whereas COX‐c and WIX‐c were resistant initially. Hypoxia‐induced drug resistance was present immediately after reoxygenation and tended to decrease with time but remained statistically significant even 42 hr after reoxygenation.
Overexpression of p53 protein in betel‐ and tobacco‐related human oral dysplasia and squamous‐cell carcinoma in India
Authors: Kaur Jasbir , Srivastava Anurag , Ralhan Ranju 
Published: February 2007

AbstractThe aetiological factors for oral cancer are not the same in India and in Western countries. Epidemiological studies have shown a correlation between high incidence of oral cancer and heavy consumption of betel and/or tobacco in the Indian population, while this stud/ indicates an association with a genetic change. The p53 tumour‐suppressor gene is the most commonly identified mutated gene in human malignancies. Expression of p53 protein was examined in premalignant and malignant oral lesions from Indian patients who were consumers of betel, areca nut and/or tobacco, using anti‐p53 monoclonal antibodies PAb 1801 and PAb 421. Cryosections from normal, premalignant or malignant oral mucosa were used for immunostaining and the observations were confirmed by immunoprecipitation. P53 protein was detected in 55% (15/27) premalignant oral lesions (leukoplakia). Strong p53‐positive staining was detected in 75% (24/32) of oral squamous‐cell carcinomas. Normal oral mucosa did not show positive p53 staining (0/24). The detection of p53 protein in premalignant oral lesions suggests that p53 aberrations are an early event in the development of oral cancer in India. The high incidence of p53 positivity in leukoplakia may be due to differences in aetiological factors. p53 overexpression in premalignant oral lesions is important in view of the significantly earlier onset of leukoplakia in the Indian population compared to the development of oral malignancy, and may be helpful in identifying lesions that are more likely to progress to malignancy. The frequency of p53 protein overexpression was high in premalignant and malignant oral lesions of patients who were heavy consumers of betel, areca nut and tobacco.
A new cancer‐associated antigen defined by a monoclonal antibody against a synthetic carbohydrate chain
Authors: Yamashita Yoshito , Chung Yong Suk , Sawada Tetsuji , Kondo Yasuyuki , Hirayama Koji , Inui Akimasa , Nakata Bunzo , Okuno Masahiro , Horie Ryuichi , Saito Takashi , Murayama Keiichi , Kannagi Reiji , Sowa Michio 
Published: February 2007

AbstractCarbohydrate antigens can be designed by referring to previously defined carbohydrate structures. We have generated a novel monoclonal antibody (MAb) (Flα‐75) against an artificially designed antigen (Flα), using organic‐synthetic chemistry methods and hybridoma technology. Flα (GalβI → 4GlcNAcβI → 6GalNAαI → Ser/Thr) belongs to core type 6 of O‐linked glycans, which has not been previously reported in human cancers. To produce antibodies against Flα, a glycolipid was synthesized which carries the carbohydrate portion of Flα on a ceramide foundation (GalβI → 4GlcNAcβI → 6GalNAcαI → Cer). The MAbs we obtained (Flα‐75, Flα‐87) specifically recognized Flα and had only a very weak or no cross‐reactivity with other glycolipids similar to Flα. We investigated the expression of Fin in human tissues, including 110 gastric cancers, 73 colon cancers and 42 pancreatic cancers. Flα was found in human cancerous tissues but not in normal adult tissues. The rate of positive staining with Flα‐75 was 80.0% for gastric cancer, 52.4% for pancreatic cancer and 38.4% for colon cancer. Flα‐75 also reacted with the tissues neighboring gastric and pancreatic tumors but not intensely. Among fetal tissues, Flα‐75 reacted with the pyloric glands of the stomach, the centro‐acinar cells of the pancreas, the convoluted tubules of the kidney and the terminal bronchioles of the lung.
Fibroblast activation protein: Purification, epitope mapping and induction by growth factors
Authors: Rettig Wolfgang J. , Su Sai L. , Fortunato Sheila R. , Scanlan Matthew J. , Mohan Raj B. K. , Garin‐Chesa Pilar , Healey John H. , Old Lloyd J. 
Published: February 2007

AbstractThe human fibroblast activation protein (FAP) defined by monoclonal antibody (MAb) F19 is a cell surface antigen expressed in reactive stromal fibroblasts of breast, colorectal, lung and other epithelial cancers. In contrast to its stroma‐specific localization in epithelial neoplasms, FAP is expressed in the malignant mesenchymal cells of bone and soft‐tissue sarcomas. FAP is transiently expressed in some fetal mesenchymal tissues but is absent or expressed at low levels in most adult tissues. FAP is induced in cultured fibroblasts and, in these cells, consists of a Mr 95,000 subunit (FAPα) carrying the F19 epitope and a non‐covalently bound Mr 105,000 subunit (FAPβ) lacking the F19 epitope. Using MAb F19 and 5 newly derived MAbs, we identify 3 distinct epitopes on FAPα and tentatively assign one epitope to FAPβ. Analysis of detergent extracts of a FAPαhighβ‐sarcoma cell line by size exclusion–high performance liquid chromatography (HPLC) revealed that FAPα does not elute as a Mr, 95,000 species but as part of a high‐molecular weight complex (Mr > 400,000) that dissociates into Mr 95,000 subunits in SDS gels. Immunoaffinity purification of FAPα followed by tryptic digestion, reversed‐phase HPLC and microsequencing identified 3 unique FAPα peptides, with 2 showing sequence similarity (23/38 identical amino acids) to segments of CD26, a T‐cell activation antigen. CD26 is a membrane‐bound enzyme (dipeptidyl aminopeptidase IV), but immunopurified FAPα has little if any dipeptidase activity with typical CD26 substrates. Finally, studies with FAPlow leptomeningeal fibroblasts revealed that transforming growth factor‐β, 12‐O‐tetradecanoyl phorbol‐13‐acetate and retinoids can upregulate FAP expression, whereas serum and several other factors had no or little effect on FAP levels. FAP and CD26 may belong to a family of structurally related but functionally distinct activation proteins that are expressed on different cell types and show unique modes of regulation in normal and malignant cells.
Therapeutic effect of adriamycin encapsulated in long‐circulating liposomes on meth‐a‐sarcoma‐bearing mice
Authors: Oku Naoto , Doi Kanako , Namba Yukihiro , Okada Shoji 
Published: February 2007

AbstractLong‐circulating liposomes modified with a uronic‐acid derivative, palmityl‐D‐glucuronide (PGIcUA), have been developed previously for the passive targeting of liposomes to tumor tissues. In this study, we examined the therapeutic effect of adriamycin (ADM) encapsulated in PGIcUA liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (Chol) and PGIcUA (molar ratio, 40/40/10) since this amount of PGIcUA was enough to endow liposomes with long‐circulating activity. Long‐circulating activity was also observed with palmityl‐D‐galacturonide (PGalUA) modified liposomes, suggesting that uronic acid plays an important role in preventing liposomes from being trapped in the reticuloendothelial system (RES). ADM was loaded in liposomes by a remote‐loading method. Free or liposomal ADM was injected i.v. into BALB/c mice bearing s.c.‐implanted Meth‐A sarcoma. The liposomal formulation was efficient for reducing tumors, prolonging survival time and curing the animals, especially in the case of large tumors where free ADM was not. Furthermore, PGIcUA liposomes were more effective than conventional liposomes containing dipalmitoylphosphatidylglycerol (DPPG) instead of PGIcUA for prolonging survival time in mire. It might therefore be appropriate to use PGIcUA liposomes as the carriers of anticancer drugs.
Therapeutic effects of D‐aspartic acid β‐hydroxamate (DAH) on friend erythroleukemia
Authors: Tournaire Roselyne , Malley Serge , Hamedi‐Sangsari Farid , Thomasset Nicole , Grange Jacques , Dore Jean François , Vila Jorge 
Published: February 2007

AbstractD‐aspartic acid β‐hydroxamate (DAH), an aspartic acid analogue, exerts anti‐tumoral activity against murine leukemia L5178Y bath in vitro and in vivo. We show here that DAH displays activity against Friend leukemia cells (FIX) in vitro: a concentration of 2 mM results in a total inhibition of cell growth. DAH is also active in vivo against Friend virus (FV‐P)‐induced erythroleukemia. Treatment with DAH, given for 95 days as a single daily i.p. injection to DBA/2 mice 3 days following FV‐P inoculation, induced a marked increase of 212% in the mean survival time (MST) of treated animals. Since FV‐P‐induced erythroleukemia is characterized by the proliferation of mature erythroid precursors, we examined the effect of DAH treatment on erythroid colony‐forming cells (CFU‐E) and observed that the number of CFU‐E per spleen was 30 times lower in DAH treated mice than in the controls. To gain further insight into the early effects of DAH treatment on the early phase of Friend disease, we examined the effects of short DAH treatment on spleen size, hematocrit and viremia in FV‐P‐infected mice. DAH treatment initiated 3 days post infection (p.i.) inhibited splenomegaly, prevented virus‐induced polycythemia, and reduced serum viremia. Late DAH treatment (18 days p.i.) induced regression of FVP‐induced disease as evidenced by reduction of spleen weight.
Effect of the nonsteroidal antiestrogen ZK 119.010 on growth and metastasis of the EnDa endometrial carcinoma
Authors: Horn Daniel W. , Vollmer Günter , Angerer Erwin Von , Schneider Martin R. 
Published: February 2007

AbstractFor patients with disseminated endometrial cancer the prognosis is poor. Radiotherapy, chemotherapy or high‐dose progestins have been of limited value in the clinic, with low response rates and a usually short duration. Because of the role of estrogen in the etiology of this disease, a rationale exists for therapies using estrogen antagonists. In order to test this strategy, we used the EnDA endometrial carcinoma of the rat recently described by us. The nonsteroidal antiestrogen ZK 119.010 inhibited the primary‐tumor growth of the s.c. implanted EnDA endometrial carcinoma by 50%, being superior to high‐dose progestin and tamoxifen (TAM). Moreover, in intact as well as in castrated estrogen (E2)‐substituted rats, ZK 119.010 substantially reduced metastatick‐tumor growth in the lymph nodes and lungs. With TAM, however, the number of lung metastases in intact and in castrated E2‐substituted rats either rose or remained stable and the weight of lymph nodes in intact rats increased. After TAM treatment, almost no low‐salt‐extractable (cytosolic) estrogen receptor (ER) was measurable in the tumor, whereas ZK 119.010 did not alter ER concentrations. The stimulation of metastatic tumor growth, as well as the loss of cytosolic ER under TAM therapy, may reflect the well‐known agonist activity of this compound in uterine tissues. ZK 119.010, however, not only lacks this agonist activity, but it exerts a strong antagonistic one. In conclusion, pure antiestrogens may help to improve treatment of endometrial cancer.
Risk assessment of tobacco, alcohol and diet in oral cancer—A case‐control study
Authors: Rao D. N. , Ganesh B. , Rao R. S. , Desai P. B. 
Published: February 2007

AbstractA retrospective case‐control study of 713 male oral‐cancer patients seen at Tata Memorial Hospital, Bombay, during 1980‐1984 was undertaken to assess the association between chewing, smoking and alcohol habits. Male controls were chosen among those persons who attended the hospital during the same period and were diagnosed as free from cancer, benign tumour and infectious disease. Statistical analysis was based on unconditional logistic regression and the confidence interval for RR was calculated using the standard error of the estimates. Established factors such as tobacco chewing and bidi smoking showed a significant association with oral cancer. For the alcohol habit, the relative risk was 1.42 and the dose‐response relationship, in terms of frequency and duration of the habit, was also observed. The illiterate group showed an almost 2‐fold significant excess risk compared to the literate group. After adjusting for confounding variables such as age, residence, illiteracy and known factors such as tobacco chewing and bidi smoking, the study has brought out the significance of a non‐vegetarian diet as a high‐risk factor for oral cancer compared to a vegetarian diet. Further studies are required to identify specific items in the non‐vegetarian diet which may be associated with oral cancer.
Expression of the co‐stimulatory molecule B7 on melanoma cells
Authors: Hersey Peter , Si Zhaoyi , Smith Melanie J. , Thomas Wayne D. 
Published: February 2007

AbstractThe induction of T‐cell responses against tumor cells is believed to depend on both recognition of antigen and receipt of co‐stimulatory signals from interaction of ligands such as B7 with its receptors CD28 or CTLA‐4 on T cells. In the present study the expression of B7 on cultured human melanoma cells was studied at the mRNA level by reverse PCR analysis and surface expression by flow cytometric analysis with monoclonal antibodies (MAbs). PCR analysis revealed mRNA for B7 in 3 of 6 (50%) cultured primary melanoma and 8 of 19 (42%) cultures of metastatic melanoma. Analysis of B7 expression by flow cytometry using the BBI MAb revealed low levels of expression in 3 of 10 melanoma that had mRNA for B7. In 2 of the latter (but not 4 other PCR+ lines) expression could be increased by culture in GM‐CSF, IL‐2, IFN‐γ and IFN‐α2. Our results indicate that although mRNA for B7 is present in 40‐50% of melanoma cell lines, expression at the protein level is at low or undetectable levels in the majority of the cell lines. Expression of B7 protein was also not detected in studies on tissue sections from 11 primary and 9 metastatic melanomas.