bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic chemotherapy in tumor‐bearing rats using high‐dose cis‐diamminedichloroplatinum(II) with low nephrotoxicity in combination with angiotensin II and sodium thiosulfate
Authors: Kobayashi Hiroaki , Hasuda Keitaro , Aoki Ken , Taniguchi Shun'Ichiro , Baba Tsuneo
Published: February 2007

Systemic chemotherapy using high‐dose DDP and its antidote, STS, was combined with the AT‐II‐induced hypertension method and evaluated for efficacy against s.c. tumors in rats. After i.v. infusion of DDP plus AT‐II for 5 min, STS was administered i.v. over a further 5 min. The rats treated with this combination chemotherapy showed normal levels of BUN and serum creatinine 4 days after the treatment, although most rats given i.v. STS after DDP without AT‐II showed severe nephrotoxicity. The absence of obvious nephrotoxicity in AT‐II‐combined chemotherapy using i.v. DDP plus post‐administered STS can be explained by a transient inhibition of DDP‐delivery to the kidney during the AT‐II‐induced hypertension. The anti‐tumor effect of this modified therapy, evaluated by inhibition of tumor growth, was superior to other treatments, as follows: concomitant i.v. administrations of DDP and STS; i.v. DDP, with or without AT‐II. The improvement in anti‐tumor effect of this combination therapy is explained by the delayed neutralization of active DDP by STS at the tumor site and the selective enhancement of DDP delivery to the tumor tissue, as produced by AT‐II. Thus, systemic chemotherapy using high‐dose DDP induced no obvious nephrotoxicity and improved the anti‐cancer effect in the case of concomitant administration of DDP plus AT‐II and the time‐delayed injection of STS.
Cell lines of human oral squamous‐cell carcinomas retaining their differentiated phenotype
Authors: Crooijmans R. P. M. A. , Schwachöfer J. H. M. , Hoogenhout J. , Merkx G. , Poels L. G. , Jap P. H. K. , Ramaekers F. C. S. , Mijnheere E. P. , Elprana D. , Thomas C. M. G.
Published: February 2007

Two cell lines from head‐and‐neck squamous‐cell carcinomas (SCC) have been established and characterized. Cell line R105 was derived from a xenografted SCC of the floor of the mouth and cell line T87/rc from a SCC of the epiglottis. Identification of individual cytokeratins 4, 5, 7, 8, 10, 13, 14, 18 and 19 led to the conclusion that both cell types had squamous characteristics and that keratinization occurred in xenografts. Ultrastructurally, junctional complexes were observed in both cell lines. Characteristic marker chromosomes were found and although both cell lines were derived from male patients, the Y chromosome was missing from all examined cells. The basic biological parameters of both cell lines were modal chromosome numbers of 59 (R105) and 60 (T87/rc), a doubling time of 60 (R105) and 45 hr (T87/rc) and a DNA index of 1.54 (R105) and 1.31 (T87/rc). The tumorigenicity of the 2 cell lines was proved by the ability to form colonies on a plastic substratum, as well as in a soft agar assay. Furthermore, the cells could produce multi‐cellular tumour spheroids, and formed tumour nodules after subcutaneous inoculation into nude mice. The R105 tumour cells appeared to be better differentiated than the T87/rc as observed by histology and immuno(histo)chemistry. Both cell lines appear to retain SCC differentiation after being xenografted into nude mice, cultured for more than 40 passages in vitro and thereafter again xenografted into nude mice.
Monosialoganglioside biosynthesis by subcellular membranes of rhabdomyosarcoma cell lines differing in metastatic potential
Authors: Liepkans V. A.
Published: February 2007

We found that rhabdomyosarcoma (RMS) subcellular membranes contain sialyltransferase activities for LcOse4Cer and GgOse4Cer acceptors. Chromatographic analyses and neuraminidase lability of the sialyltransferase products indicated that the principal site of sialylation was the non‐reducing terminal galactosyl moiety. In order to control for the effects of cell density in culture, metastatic S4T18 RMS cells and non‐metastatic F9‐4/21 RMS cells were harvested at 2 × 104 to 6 × 104 per cm2 prior to analyses. Irrespective of metastatic potential, we found that sialyltransferase‐specific activities were influenced by cell densities. F9‐4/21 cells, for example, at a density of 6 × 104, produced membranes with sialyltransferase‐specific activities to LcOse4Cer 1.9‐fold higher than cells at 2.1 × 104/cm2. Metastatic potential (predetermined in vivo) appeared to be correlated with an accelerated effect of cell density on the sialyltransferase activity to LcOse4 Cer. Metastatic S4T18 cells at 6.3 × 104/cm2 yielded membranes with sialyltransferase‐specific activities 5.4‐fold higher than membranes from cells at 1.9 × 104/cm2. Conversely, fucosyl‐transferase activities in the presence of LcOse4Cer were highest in non‐metastatic F9‐4/21 cells at low cell densities. Quantitative analyses of monosialoganglioside fractions of RMS cells were in agreement with the sialyl‐transferase studies. HPLC and HPTLC analyses demonstrated the presence of glucosamine‐containing monosialoganglioside with Rf identical with the radioactive products of LcOse4Cer sialylation, which increased 4.5‐fold on a per mg protein basis as cell densities increased in S4T18 cells in culture from 1.9 × 104/cm2 to 6.3 × 104/cm2. Plasma membrane marker Na+, K+, ATPase‐specific activity also increased in RMS metastatic cells in a manner comparable to that described for the sialyl‐transferase activity to LcOse4Cer. Our results suggest that metastatic potential is expressed in the rate of sialylation at specific membrane sites of RMS intercellular contact. We propose a process of selection for metastasis whereby specific cell surface non‐reducing galactosyl termini are recognized by intercellular transferases and lectins in the primary tumor, and the corresponding labile sialylated sites (on disseminated cells) are recognized by host neuraminidases.
Transmission of HTLV‐I to rabbits via semen and breast milk from seropositive healthy persons
Authors: Iwahara Y. , Takehara N. , Kataoka R. , Sawada T. , Ohtsuki Y. , Nakachi H. , Maehama T. , Okayama T. , Miyoshi I.
Published: February 2007

Four rabbits inoculated intravenously with milk cells from 4 post‐partum women seropositive for human T‐cell leukemia virus type 1 (HTLV‐1) and one rabbit inoculated with semen cells from a seropositive healthy man seroconverted for HTLV‐1 after 3–5 weeks but no seroconversion occurred in 2 rabbits inoculated with milk cells from a seronegative mother or with heated (56°C, 30 min) milk cells from a seropositive mother. Attempts were made to isolate HTLV‐1 from peripheral blood lymphocytes harvested 5–15 weeks after cell inoculation and cultured in the presence of interleukin‐2. An HTLV‐1‐carrying lymphoid cell line of rabbit origin was established from a rabbit inoculated with milk cells. Another long‐term culture, derived from a rabbit inoculated with semen cells, also expressed HTLV‐1 antigens and harbored virus particles. Furthermore, transfusion of 20 ml of blood from all 5 seroconverted rabbits, but not from the 2 seronegative ones, caused seroconversion in normal recipient rabbits after 4–6 weeks.
Role of glycolipids in the metastatic process: Characteristics of neutral glycolipids in clones with different metastatic potentials isolated from a murine fibrosarcoma cell line
Authors: Mannori Gianna , Cecconi Oliviero , Mugnai Gabriele , Ruggieri Salvatore
Published: February 2007

We investigated whether metastatic phenotype is associated with a characteristic glycolipid pattern. For this study, we developed a system of variants with different metastatic potentials that we isolated from the highly metastatic T3 murine fibrosarcoma line by culture in 0.3% agar or on plastic. The glycolipid profiles of T3 cells and of their highly metastatic isolates were characterized by a high level of globotriaosylceramide (Gb3ose). On the other hand, Gb3ose was reduced in a weakly metastatic clone isolated from T3 cells. A reduced level of Gb3ose was also found in a weakly metastatic subclone isolated from a highly metastatic T3 clone. Propagation of this subclone led to the emergence of a series of variants which expressed a high metastatic potential together with a high Gb3ose level. We also observed that Gb3ose was 10 times more prevalent on the cell surface in T3 cells than in a weakly metastatic clone. On the whole, these findings indicate that, in our system of metastatic cells, a high Gb3ose level correlates with metastatic phenotype. It is possible that the highly exposed Gb3ose in metastatic cells is relevant to the metastatic process in view of the role played by the unique molecular structure of this glycolipid in other models of cell‐to‐cell interaction.
Childhood cancer incidence in Queensland, 1979–88
Authors: McWhirter W. R. , Petroeschevsky A. L.
Published: February 2007

Data on the incidence of childhood cancer in Queensland during the 10‐year period 1979–88 are presented. During this period, 786 cases were registered. The average annual crude and age‐standardized (to the world population) incidence rates for both sexes were 12.63 and 13.30 per 100,000 respectively. The incidence of cancer in males is unusually high, as is the sex ratio of 1.57. ALL accounted for 78% of all leukaemias. There appears to have been a decline in the incidence of Hodgkin's disease, especially in older children, compared with an earlier Queensland series. Ewing's tumour remains commoner than osteosarcoma. Some modifications to the classification scheme for childhood cancer are proposed. The most important of these is the omission of Langerhans‐cell histiocytosis, which is not now regarded as a neoplasm.
Increased risk of urothelial cancer in Stockholm during 1985‐87 after exposure to benzene and exhausts
Authors: Steineck Gunnar , Plato Nils , Gerhardsson Maria , Norell Staffan E. , Hogstedt Christer
Published: February 2007

In a population‐based case‐referent study of urothelial cancer in Stockholm during 1985–87, information was obtained from 80% of 320 identified male cases and 79% of 363 selected male referents. Industrial exposures were assessed for each subject by an industrial hygienist on the basis of questionnaire data. Exposure to benzene (any annual dose) gave a relative risk (with 95% confidence interval) of 2.0 (1.0–3.8). The highest risk was seen for a high annual dose. Subjects exposed to both diesel and petrol exhausts (moderate/high annual dose) had a relative risk of 7.1 (0.9–58.8). However, adjusting for benzene changed the relative risk to 5.1 (0.6–43.6). It might be rewarding to consider whether benzene from petrol confounds the associations previously suggested between exhausts and urothelial cancer. Exposure to polychlorinated biphenyls (PCB) gave a relative risk of 3.3 (0.6–18.4).
Amplification and overexpression of the epidermal growth factor receptor gene in human renal‐cell carcinoma
Authors: Ishikawa Jiro , Maeda Sakan , Umezu Kei‐Ichi , Sugiyama Taketoshi , Kamidono Sadao
Published: February 2007

We examined 22 cases of renal‐cell carcinoma (RCC) for structural alterations of the epidermal growth factor receptor (EGFR) gene and found gene amplification in one case of high‐stage‐high‐grade RCC. Dot blot analysis of the total RNA from tumorous and normal kidney tissues revealed overexpression of the EGFR gene in 12 of 20 (60%) cases of RCC. The highest expression was observed in the geneamplified case. No correlation was observed between the level of EGFR mRNA and tumor stage or grade. Northern blot analysis revealed normal 10‐ and 5.6‐kb EGFR mRNA bands in RCC. Our data indicate that gene amplification of the EGFR gene is one of the molecular mechanisms of its overexpression in a subset of RCCs.
Occupational and other non‐dietary risk factors for nasopharyngeal carcinoma in Guangzhou, China
Authors: Yu Mimi C. , Garabrant David H. , Huang Teng‐Bo , Henderson Brian E.
Published: February 2007

We conducted interviews on 306 histologically confirmed incident cases of nasopharyngeal carcinoma (NPC) occurring in residents of Guangzhou City, China, who were under the age of 50, and an equal number of age‐, sex‐, and neighborhood‐matched controls. We also interviewed 110 mothers of patients under 45 and 139 mothers of controls who were matched to patients under age 45, to obtain information on childhood exposures of study subjects. Occupational exposure to products of combustion (RR = 2.4, p = 0.001) and cotton dust (RR = 0.3, P = 0.01) was independently related to risk of NPC. Use of tobacco products showed a moderate association with NPC; a lifetime exposure of 30+ pack‐year equivalents conferred a 2‐fold increased risk. A history of chronic ear or nose condition (rhinitis, sinusitis, nasal polyp, otitis media) was another risk factor for NPC (RR = 2.2, p < 0.0005), and 18 cases compared to 3 controls had a first‐degree relative with NPC (RR = 6.0, p = 0.001).
Changes in glycolipid expression in human testicular tumor
Authors: Ohyama Chikara , Fukushi Yasuo , Satoh Makoto , Saitoh Seiichi , Orikasa Seiichi , Nudelman Edward , Straud Mark , Hakomori Sen‐Itiroh
Published: February 2007

Glycolipids were extracted from testicular tumor tissues of 13 patients, and their pattern of expression compared with that of normal testicular tissue. The most conspicuous and consistent change in the tumor extracts was marked accumulation of CTH (ceramide trihexoside). Structural analysis by enzyme cleavage showed that CTH which accumulated in the tumor tissue was Gb3 (Galαl‐4Galßl‐4Glcßl‐Cer). Immunohistochemistry using anti‐Gb3 monoclonal antibody (MAb) (lA4) also indicated massive accumulation of Gb3 in the tumor tissue. Gb3 may be a new marker of testicular tumors, especially seminomas, for which useful markers are so far lacking.
Incidence of childhood cancer in La Plata, Argentina, 1977–1987
Authors: Drut Ricardo , Hernández Ana , Pollono Daniel
Published: February 2007

Incidence data on malignant tumors in children aged 0–14 for the period 1977–87 were calculated in La Plata, Argentina. The number of children living in La Plata was 151,085. The overall incidence of malignant tumors was 106.5 per million (127.4 for males and 83.4 for females). Leukemia (30.5%), lymphoma (15.2%) and central nervous system (14.1%) comprised 60% of all tumors. The relative frequency of histologic types was similar to the pattern recognized in other countries of Latin America and different from that reported in North America and Europe where brain tumors rank second. A high incidence of orchioblastoma (infantile embryonal carcinoma) present in this survey can only be substantiated after a longer period of study.
Maintenance on extracellular matrix and expression of heparanase activity by human ovarian carcinoma cells from biopsy specimens
Authors: Peretz Tamar , Antebi Shaul U. , Beller Uziel , Horowitz Aviva T. , Fuks Zvi , Vlodavsky Israel
Published: February 2007

A routine procedure has been developed for the isolation and maintenance in culture of human ovarian carcinoma cells derived from biopsy specimens. Cell attachment, plating efficiency and initial outgrowth were greatly improved by seeding the cells on a basement‐membrane‐like extracellular matrix (ECM) deposited by cultured corneal endothelial cells. These effects were most significant in serum‐free conditions which markedly reduced the rate of cell attachment and growth on regular tissue culture plastic. In 60–80% of the cases and regardless of the patient's age, cells cultured on ECM in the absence of serum divided actively and formed a tightly packed epithelial cell monolayer. Fibroblast overgrowth and cell detachment often occurred on ECM in the presence of serum. Incubation of the human ovarian carcinoma cells with sulfate‐labelled ECM, resulted in the release of heparan sulfate degradation fragments, 4‐ to 7‐fold smaller than intact heparan sulfate side chains. This degradation was brought about by endoglycosidase (heparanase) activity expressed to a higher extent by cells that were first maintained in primary cultures as compared with cell aggregates taken directly from the biopsy specimen. In most cases, cells derived from metastatic tumors expressed a higher heparanase activity than cells from the primary ovarian tumor. This result corroborates previous studies, performed with cell lines, on the possible involvement of heparanase in tumor cell invasion and metastasis.
Immunophenotyping of childhood astrocytomas with a library of monoclonal antibodies
Authors: Bodey Bela , Zeltzer Paul M. , Saldivar Victor , Kemshead John
Published: February 2007

Immunophenotype (IP) analysis of 14 childhood glial tumors was performed with a library of 16 monoclonal antibodies (MAbs) using biotin‐streptavidin‐alkaline phosphatase immunohistochemical detection technique. Presence of glial or neuronal differentiated cells within the tumors was evaluated with MAbs against cell‐lineage‐specific markers: high‐, medium‐ and low‐molecular‐weight neurofilament protein (NFP) and glial fibrillary acidic protein (GFAP). Intense expression of GFAP was demonstrated in 14/14 astrocytomas. The three NFs were detected in 10–50% of the cells in 6/14 cases. The pan‐neuro‐ectodermal antigen defined by MAb UJ 13/A was present in 7/14 astrocytomas on more than 10% of the cells. Thy‐1 was expressed in 14/14 tumors on more than 50% of their cells. The GQ ganglioside antigen detected by MAB A2B5, was found in 12/14 tumors. Shared antigens exist among morphologically benign and malignant glial tumor cells and leukocytes detectable with the following four MAbs: Thy‐1, Pl 153/3, UJ 308 and anti‐HLe, common leukocyte antigen (CLA). CLA‐expressing cells were demonstrated in 8/12 astrocytomas, and in 4/12 cases more than 90% of the cells were positive. We have shown that cells within childhood astrocytomas can express neuronal IP. The most common expressed phenotype for glial tumors was: GFAP+, Thy‐1+, A2B5+, UJ 167.11+, UJ 223.8+, NF (H,M)+, UJ 13/A+, UJ 127.11−, and NF (L)−.
Immunochemical localization of heparanase in mouse and human melanomas
Authors: Jin Li , Nakajima Motowo , Nicolson Garth L.
Published: February 2007

Heparanase, an endo‐β‐D‐glucuronidase, has been associated with melanoma metastasis. Polyclonal antibodies directed against the murine N‐terminal heparanase peptide detected a Mr ∼ 97,000 protein on SDS‐PAGE of mouse melanoma and human melanoma cell lysates. In an indirect immunocytochemical study, human A375‐SM and mouse B16‐BL6 melanoma cells were stained with the anti‐heparanase antibodies. Heparanase antigen was localized in the cytoplasm of permeabilized melanoma cells as well as at the cell surface of unpermeabilized cells. Immunohistochemical staining of frozen sections from syngeneic mouse lungs containing micrometastases of B16‐BL6 melanoma demonstrated heparanase localized in metastatic melanoma cells. Similar studies using frozen sections of malignant melanomas resected from patients indicated that heparanase is localized in invading melanoma cells. Our studies suggest that (a) the N‐terminus of the heparanase molecule in mouse and human is antigenically related; (b) heparanase antigens are localized at the cell surface and in the cytoplasm of metastatic human and mouse melanoma cells; and (c) heparanase antigens are enriched in invasive and metastatic murine and human melanomas in vivo.
Tumor necrosis factor induces necrosis of human carcinoma xenografts in the presence of tricyclodecan‐9‐yl‐xanthogenate and lauric acid
Authors: Amtmann Eberhard , Sauer Gerhard
Published: February 2007

Recombinant human tumor necrosis factor (rh TNF) when administered intravenously together with the phospholipase C inhibitor tricyclodecan‐9‐yl‐xanthogenate (D609) and lauric acid (C12), leads to the partial regression of various human tumor transplants in athymic mice. Extensive necrosis occurred after a single intravenous infusion, with no detectable side effects. TNF‐mediated cytotoxicity was found to be correlated with the depletion of energy in HeLa cells. The activity of rh TNF was enhanced by the absence of glucose, while it was reduced by addition of extraneous ATP. In the presence of rh TNF, D609, and C12, cellular energy metabolism was almost completely switched to glycolysis. Under these conditions the cytocidal activity of rh TNF on HeLa cells was amplified at least 60‐fold.
Extraction of type‐IV collagenase/gelatinase from plasma membranes of human cancer cells
Authors: Zucker Stanley , Moll Ute M. , Lysik Rita M. , Dimassimo Elizabeth I. , Stetler‐Stevenson William G. , Liotta Lance A. , Schwedes Janine W.
Published: February 2007

Tumor proteinases are considered to be important in the process of cancer invasion and metastasis. We have proposed that the surface membrane localization of these proteinases places them in an optimal site to facilitate the invasion of surrounding extracellular matrix. In this study, we have used the organic solvent, n‐butanol, and the detergent, n‐octylglucoside, to sequentially extract metalloproteinases from crude plasma membranes of human RWP‐1 pancreatic cancer cells. Anion exchange chromatography and gel permeation chromatography were employed to further purify enzymes with the capacity to degrade gelatin, type‐IV collagen, and carboxymethylated transferrin. Gelatin zymography was used to demonstrate proteinase bands of 92, 70 and 62kDa. Immunoblotting of solubilized, partially purified pancreatic cancer plasma membrane proteins using polyclonal rabbit antibodies, which have specificity for type‐IV collagenase/ gelatinase, resulted in the recognition of a 70‐kDa protein, but not the 92‐kDa gelatinase. A type‐IV collagenase/gelatinase of 68kDa was similarly identified in A2058 human melanoma cancer cell plasma membranes.
Expression of ras oncogene leads to down‐regulation of protein kinase C
Authors: Haliotis Tina , Trimble William , Chow Sue , Bull Shelley , Mills Gordon , Girard Peggy , Kuo J. F. , Hozumi Nobumichi
Published: February 2007

The effect of mutated c‐Ha‐ras expression on Ca2+ and phospholipid‐dependent protein kinase C (PKC) activity during the process of transformation was analysed using an inducible metallothionein‐ras hybrid oncogene system. A close correlation was found between the timing of ras expression and the loss of PKC enzymatic activity measured in a cell‐free system. Examination of the subcellular distribution of the enzyme in inducible and constitutive ras‐transformants revealed that expression of ras was associated with an apparent translocation of PKC to the plasma membrane concomitant with down‐regulation of PKC enzymatic activity in particulate as well as cytosolic fractions. Quantitation of PKC protein utilizing a PKC‐specific antiserum showed that ras expression was associated with a decrease in the total amount of PKC protein present in the cell. We conclude that transformation by c‐Ha‐ras is accompanied by down‐regulation of PKC activity and that the basis of this effect may, to a large extent, lie in the down‐regulation of the amount of PKC protein.
Intraperitoneal radio‐localization of tumors pre‐targeted by biotinylated monoclonal antibodies
Authors: Paganelli G. , Pervez S. , Siccardi A. G. , Rowlinson G. , Deleide G. , Chiolerio F. , Malcovati M. , Scassellati G. A. , Epenetos A. A.
Published: February 2007

We describe 2‐step and 3‐step strategies for intraperitoneal tumor radio‐localization by means of monoclonal antibodies (MAbs). Nude mice bearing intraperitoneal human colon carcinoma tumors were injected i.p. with biotinylated MAb AUAI, followed 24 hr later by radioiodinated streptavidin (2‐step). The uptake of radioactivity in tumor and normal tissues was measured 4 hr after injection of radioactive compound. A 3‐step strategy consisted in administering biotinylated antibody, cold avidin after 24 hr and 111In‐labelled biotin after a further 4 hr; mice were then killed 2 hr later. Tumor localization of intraperitoneally‐administered biotinylated antibody and direct targeting of radioactive streptavidin to biotinylated antibody bound to tumor sites were demonstrated using immunohistochemistry and autoradiography. Our results show that (i) the 2‐step approach increased the percentage of radioactivity uptake by tumor with respect to directly labelled antibodies (24% vs. 6%) and improved the tumor/non‐tumor ratio; (ii) the 3‐step approach allowed faster blood clearance of the radioactive probe (111In‐biotin) and yielded high tumor/non‐tumor ratios. “Pre‐targeting” methods appear to have advantages over the conventional 1‐step approach with directly radiolabelled antibody.
A synthetic thymic hormone, THF‐γ2, repairs immunodeficiency of mice cured of plasmacytoma by melphalan
Authors: Ophir R. , Pecht M. , Rashid G. , Halperin D. , Lourie S. , Burstein Y. , Ben‐Efraim S. , Trainin S.
Published: February 2007

BALB/c mice cured of large MOPC‐315 plasmacytomas by melphalan remain deficient in their spleen T‐cell functions. This was manifested by impairment of the allogeneic and the antibody responses in vitro to SRBC and in decreased numbers of T‐cells including their subsets CD4 and CD8. IL‐2 production and specific cytotoxicity against MOPC‐315 tumor cells were, on the other hand, maintained. Treatment of these cured mice by in‐vivo administration of THF‐γ2, an octapeptide from calf thymus, repaired these deficits. This was evidenced by in vitro tests with spleen cells which manifested an increased allogeneic response and elevated generation of primary antibody response, restoration of T‐cell subpopulations to normal and an enhanced IL‐2 production above normal levels. The potential use of THF‐γ2 as supportive therapy in cancer treatment is suggested.
Injectable contraceptives and risk of invasive cervical cancer: Evidence of an association
Authors: Herrero Rolando , Brinton Louise A. , Reeves William C. , Brenes Maria M. , De Britton Rosa C. , Tenorio Francisco , Gaitan Eduardo
Published: February 2007

In a case‐control study conducted in Latin America, the relationship of injectable contraceptive (IC) use to risk of in vasive cervical cancer was analyzed while controlling for a variety of other risk factors, including female and spouse sexual behavior and infection with human papillomaviruses (HPV). Thirty‐two cases and 82 controls reported ever having used IC. Women reporting use of IC for less than 5 years had an adjusted RR of 0.5 (95% CI = 0.3‐0.9), but users for 5 or more years had an RR of 2.4 (95% Cl = 1.0‐5.7). The effect of prolonged 1C use was stronger for women reporting first use 10 or more years before interview (adjusted RR = 3.4, 95% Cl = 1.1‐24.9) and more than 5 years since last use (adjusted RR = 5.3, 95% Cl = 1.1‐10.0). Cervical cancer risk associated with prolonged IC use was particularly high among women who reported never having had a Pap smear or having had one 2 or more years before interview (adjusted RR = 6.3, 95% CI = 2.1‐18.7). The reduced cervical cancer risk associated with short‐term use of IC may reflect intensive Pap smear screening as the method is initiated. Although hampered by small numbers, these results suggest an adverse effect of prolonged IC use on cervical cancer risk, particularly among women who cease participation in screening programs after terminating usage, and indicate that long‐term IC users should be monitored for cervical disease until more conclusive results are available.
Frequency of meat and fish intake and risk of breast cancer in a prospective study of 14,500 norwegian women
Authors: Vatten Lars J. , Solvoll Kari , Løken Elin B.
Published: February 2007

The association between the frequency of meat and fish intake and the incidence rate of breast cancer has been ana lyzed in 152 incident cases that developed among 14,500 Nor wegian women during 11 to 14 years of follow‐up. At the time of dietary inquiry they were between 35 and 51 years of age. A positive association was observed between the frequency of overall meat intake and breast cancer risk. There was an age‐adjusted incidence rate ratio (IRR) of 1.8 (95% confidence limits, 1.1 and 3.1) for women who had a main meal with meat 5 times or more per week compared to women who had 2 meat dinners or less per week, and this association displayed a linear trend (2 trend = 4.30, p = 0.04). No association was detected between the overall frequency of fish for dinner and breast cancer risk (2 trend = 1.39, p = 0.24), but there was an inverse relation with the frequency of main meals contain ing fish in poached form. The age‐adjusted IRR was 0.7 (95% confidence limits, 0.4 and 1.0) for women who had poached fish for dinner at least 5 times per month compared to women who had fish in this form twice monthly or less often (2 trend = 3.56, p = 0.06). The positive association with meat may be in accordance with the hypothesis that dietary fat increases the risk of breast cancer. Although there was no association with overall fish intake, the inverse relation with poached fish might deserve further investigation.
Bimodal relationship between invasion of the amniotic membrane and plasminogen activator activity
Authors: Tsuboi Ryoji , Rifkin Daniel B.
Published: February 2007

Three human tumor cell lines, Bowes' melanoma, HT1080 and Osmond cells, were characterized for their abillty to invade the amniotic membrane and their production of plasminogen activator. Bowes' melanoma cells, which release large amounts of tissue plasminogen activator (tPA), were poorly invasive on the amniotic membrane. The addition of plasmin inhibitors, anti‐tPA antibody or tissue inhibitor of metalloproteinase (TIMP) to the amnion assay enhanced invasiveness. The depletion of plasminogen from the growth medium also enhanced the degree of invasiveness. Similarly, HT1080 cells, which produce high levels of urokinase‐type plasminogen activator (uPA), were poorly invasive under standard conditions but invasion was enhanced by plasmin inhibitors or anti‐uPA antibodies. Conversely, Osmond cells, which produce low levels of uPA, were very invasive on the amniotic membrane. Invasion by these cells was blocked by the addition of plasmin inhibitors or anti‐uPA antibodies to the amnion assay. These results suggest that invasion requires only a minimum level of PA activity and that, as PA production exceeds this optimal level, the degree of invasion decreases. We propose that high levels of plasmin, generated by the tPA or uPA secreted by the cells, may cause uncontrolled matrix degradation and interrupt the interaction of cells and matrix in the early stages of invasion. The inhibition of excessive plasmin activity may stabilize and increase cell matrix contacts and result in an enhancement of invasion.
Anti‐proliferative effects of tumor necrosis factor, gamma interferon and 5‐fluorouracil on human colorectal carcinoma cell lines
Authors: Schiller Joan H. , Bittner Gerard
Published: February 2007

We have previously utilized a bank of diverse human colorectal carcinoma cell lines to assess the synergistic antiproliferative effect of tumor necrosis factor (TNF) and IFN‐gamma (IFN‐γ) in combination. In this study, we used 3 of these cell lines (HCT 116, SKCOI and VACO 9P) to study the growth‐inhibitory effects of TNF and IFN‐γ (TNF/IFN‐γ) on these cells when administered in conjunction with 5‐fluorouracil (5‐FU). All 3 cell lines were sensitive to suprapharmacologic concentrations of 5‐FU. However, the 3 lines varied in their sensitivities to clinically achievable concentrations of 5‐FU. Concentrations of 0.1 μg/ml of 5‐FU administered for 96 hr, and 50 μg/ml administered for I hr, inhibited the growth of HCT 116 cells by 20% and 77%, that of SKCOI cells by 25% and 66%, and that of VACO 9P cells by 25% and 55%, respectively. All 3 cell lines were sensitive to the anti‐proliferative effects of TNF/IFN‐γ in a dose‐dependent and duration‐dependent fashion. TNF/IFN‐γ was administered for I hr every other day on days 1, 3 and 5 to the 3 cell lines. Cells were also exposed to 5‐FU, administered either concomitantly for 96 hr, or for I hr on day I. The addition of TNF/IFN‐γ to clinically achievable concentrations of 5‐FU in both schedules resulted in additive cytotoxicity. For example, the addition of 10 ng/ml of both TNF and IFN‐γ to 96 hr of 0.1 μg/ml 5‐FU resulted in 10%, 5%, and 20% of control growth for the HCT 116 cell line, SKCOI cell line, and VACO 9P cell line, respectively. The addition of 10 ng/ml of both TNF and IFN‐γ to I hr of 50 μg/ml of 5‐FU inhibited all cell growth in all 3 cell lines. We conclude that TNF/IFN‐γ and 5‐FU can be combined to achieve higher anti‐tumor activity than either 5‐FU or TNF/IFN‐γ alone in this in vitro model, that the 3‐drug combination has potent growth‐inhibitory effects at pharmacologic concentrations which are not schedule‐dependent, and that this combination warrants further study in clinical trials.
Pharmacological modification of multi‐drug resistance (mdr) in vitro detected by a novel fluorometric microculture cytotoxicity assay. Reversal of resistance and selective cytotoxic actions of cyclosporin a and verapamil on mdr leukemia t‐cells
Authors: Larsson Rolf , Nygren Peter
Published: February 2007

A novel fluorometric microculture cytotoxicity assay (FMCA), based on measurements of fluorescein diacetate (FDA) hydrolysis and DNA staining by Hoechst 33342, was used for drug sensitivity testing and detection of resistance reversal in acute lymphoblastic leukemia (ALL) cell lines. The 72‐hr assay was found to be sensitive, reproducible and linearly related to the number of viable cells within a broad range of cell concentrations. At clinically achievable drug concentrations, the calcium channel blocker Verapamil (ver) and the immunosuppressant Cyclosporin A (csA) were found to partly reverse acquired Vincristine (vcr) resistance in multidrug resistant (MDR) T‐ALL LI00 cells with little or no effect on the drug‐sensitive parental LO cell line. By combining the fluorometric indices, we found that low concentrations of csA were growth‐inhibitory, whereas higher concentrations (>IOμg/ml) were progressively cytotoxic for drug‐sensitive LO cells. In MDR LlOO cells, on the other hand, csA produced significant cell kill even at low drug concentrations. Ver had no effects on sensitive LO cells but showed considerable cytotoxic action towards MDR LIOO cells. There was no apparent relationship between drug reversal of vcr resistance and the cytotoxic actions of the drug per se since the calcium channel blocker diltiazem (dil) significantly potentiated the actions of vcr on MDR LIOO cells without being more toxic to these cells (compared to vcr‐sensitive LO cells).
Selection of a dtpa chelate conjugate for monoclonal antibody targeting to a human colonic tumor in nude mice
Authors: Sharkey Robert M. , Motta‐Hennessy Cecilia , Gansow Otto A. , Brechbiel Martin W. , Fand Irwin , Griffiths Gary L. , Jones Anastasia L. , Goldenberg David M.
Published: February 2007

Our previous studies with a 90Y‐labelled antibody against carcinoembryonic antigen (CEA) conjugated to the cyclic anhydride‐DTPA (CA‐DTPA) indicated that the accretion of 90Y in the bone may limit the application of 90Y‐labelled antibodies for therapy. In this report, we have compared the tumor targeting of CA‐DTPA‐conjugated antibody to antibody conjugated with 4 isothiocyanatobenzyl (ITC‐Bz) derivatives of DTPA in nude mice bearing a human colonic tumor xenograft. In biodistribution studies using an 111In‐labelled anti‐CEA murine monoclonal antibody (MAb), the CA‐DTPA‐conjugated MAb showed lower tumor uptake, faster blood clearance, and higher accretion in the liver than any of the 4 ITC‐Bz‐DTPA‐conjugated MAbs. There were smaller differences among the 4 ITC‐Bz‐DTPA conjugates. Whole‐body autoradiography of animals given 90Y‐MAb prepared with the CA‐DTPA or the ITC‐Bz‐DTPA showed less radioactivity in the bone with the ITC‐Bz‐DTPA‐MAb than the CA‐DTPA‐MAb. 90Y uptake in the bone corresponded with regions of low proliferative activity as defined by 3H‐labelled thymidine, suggesting that the 90Y was in the cortex rather than the marrow. These studies clearly show an advantage of the ITC‐Bz‐DTPA derivatives for 90Y and 111In labelling of MAbs.
Inhibitory effect of selenium on hamster pancreatic cancer induction by n′‐nitrosobis(2‐oxopropyl)amine
Authors: Kise Yoshifumi , Yamamura Manabu , Kogata Munehisa , Uetsuji Shoji , Takada Hideho , Hioki Koshiro , Yamamoto Masakatsu
Published: February 2007

The effect of selenium intake on the development of pan creatic cancer was investigated in female Syrian golden ham sters. Four‐week‐old hamsters were divided into 2 groups ac cording to the selenium level in their drinking water and were fed a purified diet containing less than 0.05 ppm selenium. Starting 4 weeks later, groups received 10 s. c. injections at weekly intervals of N′‐nitrosobis(2‐oxopropyl)amine (BOP) dissolved in saline, while controls received saline alone. When the animals were killed 18 weeks after the last injection, pal pable tumors were less frequent in the high‐selenium group than in animals receiving low‐selenium supplement, the num bers of histologically diagnosed cancerous lesions also being significantly reduced by high selenium intake. The selenium level and glutathione peroxidase activity in serum and pan creas were significantly greater in the high‐selenium group. Moreover, selenium levels and glutathione peroxidase activ ity were both significantly higher in tumor‐bearing tissue. The results suggest that glutathione peroxidase is involved as an intermediate factor in prevention of carcinogenesis by sele nium.
Enhancement of fluorinated pyrimidine‐induced cytotoxicity by leucovorin in human lung cancer cell lines
Authors: Tsai Chun‐Ming , Gazdar Adi F. , Allegra Carmen , Perng Reury‐Perng , Kramer Barnett S.
Published: February 2007

Reduced folates have been shown to increase the cytotoxicity of 5‐fluorouracil (FUra) by stabilizing the fluorodeoxyuridine monophosphate: thymidylate synthase complex, thus increasing the block in the DNA synthetic pathway. Using an in vitro tetrazolium colorimetric (MTT) cytotoxic assay, we tested the effects of FUra and 5‐fluorodeoxyuridine (FUdR) with and without leucovorin (LV) on a panel of 7 human lung cancer cell lines. LV at a concentration of 20 μM enhanced the cytotoxicity of FUra and of FUdR in all of the cell lines. Quantitatively, LV had a higher degree of enhancement on FUdR than on FUra cytotoxicity in 6 cell lines. There was equivalent enhancement in the only remaining line. The differential effects of LV on the cytotoxicity of FUra vs. FUdR in these lung carcinoma lines contrasts with a quantitatively similar enhancement of cytotoxicity between FUra and FUdR in colon cancer lines previously reported from our laboratory. This suggests that the metabolism of FUra may be different in these lung cancer cell lines.
Secreted phosphoprotein mrna is induced during multi‐stage carcinogenesis in mouse skin and correlates with the metastatic potential of murine fibroblasts
Authors: Craig Ann Marie , Tim Bowden G. , Chambers Ann F. , Spearman Maureen A. , Greenberg Amold H. , Wright Jim A. , McLeod Marilyn , Denhardt David T.
Published: February 2007

Secreted phosphoprotein I (SPP), also known as 2ar, osteopontin, 44‐kDa bone phosphoprotein, bone sialoprotein I, and transformation‐related phosphoprotein, is a 41.5‐kDa glycosylated phosphoprotein secreted by many mammalian cell lines and expressed in a limited set of tissues. Using a cDNA probe, we found that SPP mRNA, which is barely detectable in normal mouse epidermis, was expressed at moderate‐to‐high levels in 2 of 3 epidermal papillomas and at consistently high levels in 7 of 7 squamous‐cell carcinomas induced by an initiation‐promotion regimen. This contrasts with the transient induction we had previously observed after a single application of the tumor promoter 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). In a set of 5 independently isolated T24‐H‐ras‐transfected mouse C3H 10T1/2 cell lines, the levels of SPP mRNA correlated well with ras mRNA levels and with both experimental and spontaneous metastatic ability. SPP mRNA expression was also elevated in a derivative of mouse LTA cells transfected with genomic DNA from Bl6FI melanoma cells and selected for increased experimental metastatic ability in the chick embryo. This apparent association of SPP expression with invasion, progression and metastasis, along with the presence of a functional ArgGlyAsp (RGD) cell adhesion site in SPP (osteopontin), leads us to propose that SPP may act as an autocrine adhesion factor for tumor cells.
Height and weight in relation to uterine corpus cancer in norway morbidity and mortality. A follow‐up study of 570,000 women in Norway
Authors: Tretli Steinar , Magnus Knut
Published: February 2007

The height and weight of 570,000 Norwegian women, aged 30‐69 years, were measured and the subjects were then followed up for 6‐18 years with regard to uterine corpus cancer morbidity and mortality. The analysis reveals that both height and Quetelet's index are risk factors for uterine corpus cancer. The risk for women belonging to the 5th quintile of both height and Quetelet's index is 3.2 times higher than the risk for women in the 1st quintile of both factors. It is argued that both height and Quetelet's index express a common etiological mechanism and that this mechanism is probably connected to the early phase of the disease. Body size expressed through body surface area reveals about the same strength of association as Quetelet's index. It is calculated that if women in the 5th quintile of Quetelet's index belonged to the 4th quintile instead, there would be about 10% fewer cases of uterine corpus cancer.
Cancer incidence correlations: Genital, urinary and some tobacco‐related cancers
Authors: Bosch F. X. , Cardis E.
Published: February 2007

Bivariate correlations between sex‐specific age‐adjusted incidence rates of 10 genital and urinary tract cancer sites and lung cancer were calculated. The data base used was that published in the 5th edition of the series Cancer incidence in five continents. The purpose of the analyses was to test the consistency of the data with the hypothesis of a common risk factor for genital cancers and other cancers of the urinary tract and for lung and genital cancers. The results indicate that the incidence of cervical cancer is strongly correlated with that of cancer of the penis, of other cancers of the female genital tract and of chorioepithelioma. In countries at low/intermediate risk for cervical cancer (mostly developed Western countries), the incidence of cervical cancer is also correlated with that of lung cancer in males. The incidence of male lung cancer is, moreover, strongly correlated with cancers of the prostate, penis, testis, bladder and other urinary tract cancers. These analyses support the views that: urogenital cancers in both sexes might share (a) common risk factor (s), which may be certain types of human papilloma‐virus; and that cigarette smoking is likely to be a risk factor for most of these cancers in countries where the use of tobacco has been widespread for a long time. Other suggestive etiological conclusions about less well‐studied cancer sites are also presented.
Changes in glycosaminoglycan synthesis and in heparan sulfate deposition in human colorectal adenocarcinomas
Authors: Bouziges Françoise , Simon‐Assmann P. , Leberquier C. , Marescaux J. , Bellocq J. P. , Haffen K. , Kedinger M.
Published: February 2007

Biosynthesis of glycosaminoglycans (GAGs) was studied in morphologically normal colonic mucosa, in peritumoral and tumoral areas, and in colorectal polyps of tumor‐bearing patients. After GAG purification, overall biosynthesis was determined: the general trend was a decrease in GAG production in neoplastic colon, lowest GAG synthesis being observed in Dukes' stage C tumors. Separation by ion‐exchange chromatography of various GAG species and further characterization revealed the presence of hyaluronic acid (HA) and heparan sulfate (HS) molecules in all specimens studied. Chondroitin‐4 sulfate (CS4) was occasionally found in tumor samples. The relative proportion of HA and HS was modified in tumor tissue: i. e. increased HA and decreased HS were observed. Differences in DEAE‐chromatographic behavior were obvious in pathological samples as compared to controls, the hydrodynamic form of HA and the charge density of HS being decreased. The latter could be attributed to undersulfatation of HS molecules. Immunocytochemical detection of HS proteoglycan molecules revealed regular and bright labelling at epithelial‐stromal interface in control samples. In pathological samples, staining was patchy and discontinuous, showing large areas of basement membrane interruption.
Interaction of human immunodeficiency and papilloma viruses: Association with anal epithelial abnormality in homosexual men
Authors: Caussy Deoraj , Goedert James J. , Palefsky Joel , Gonzales John , Rabkin Charles S. , Digioia Richard A. , Sanchez William C. , Grossman Ronald J. , Colclough Ginga , Wiktor Stefan Z. , Krämer Alexander , Biggar Robert J. , Blatiner William A.
Published: February 2007

During the 7th annual follow‐up of our cohort of homosexual men in 1989, we tested the hypotheses that infection with human immunodeficiency virus (HIV) may enhance the expression of human papilloma virus (HPV) and that the development of anal epithelial abnormality is related to a biologic interaction between these two viruses. Overall, 41 (39%) of the 105 men had anal swabs positive for one or more genotypes of HPV 6/11, 16/18 or 31/33/35. Twenty‐three (53%) of the 43 HIV‐positive subjects harbored HPV compared to 18 (29%) of the 64 HIV‐negative subjects (p = 0.012), including higher prevalence rates for HPV genotypes 16/18 (p = 0.01), 6/11 (p = 0.007), and 31/33/35 (p = 0.07). Multivariate logistic regression analysis of the HIV‐positive subjects showed low CD4+ cell counts to be an independent risk factor for detection of HPV (p = 0.04) and in particular for HPV genotypes 31/33/35 (p = 0.02) and 6/11 (p = 0.07). In contrast, similar analysis of the HIV‐negative subset showed that a positive antibody test for syphilis was associated with HPV (p = 0.03). Anal epithelial abnormalities were found in 13 (14%) of 92 technically adequate cytologic smears and were strongly associated with detection of any HPV genotypes by the dot‐blot method (p = 0.01), and in particular with HPV genotypes 6/11 (p = 0.001). None of 15 subjects with HPV detected only by PCR had anal epithelial abnormality. We propose a viral interaction model, in which HIV‐related immune deficiency allows reactivation of HPV, with a subsequent or concomitant appearance of epithelial abnormality.
Fusion of rous‐sarcoma‐virus‐transformed rat cells to morphologically normal human or rat cells results in transcriptional suppression of the provirus that depends on its chromosomal integration site
Authors: Green A. R. , Poole C. J. , Povey S. M. , Rowe D. , Searle S. , Wyke J. A.
Published: February 2007

The fusion of a Rous sarcoma virus (RSV)‐transformed rat fibroblast clone to at least 2 different human cell types reproducibly produces phenotypically normal hybrids. Analysis of such hybrids reveals that proviral silence is the result of transcriptional down‐regulation, presumably by a trans‐acting human molecule. Furthermore, this phenomenon seems to be strongly influenced by the proviral chromosomal integration site and its imposition may entail a mechanism that is required only transiently.