bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromogranin‐a expression in gastric and colon cancer tissues
Authors: Park Jae‐Gahb , Choe Ghee Young , Helman Lee J. , Gazdar Adi F. , Yang Han‐Kwang , Kim Jin‐Pok , Park Seong Hoe , Kim Yong Il 
Published: February 2007

AbstractWe studied the expression of chromogranin A (CgA) in human gastric (n = 17) and colorectal (n = 18) adenocarcinomas by nucleic acid hybridization and immunohistochemical analyses using a specific monoclonal antibody (MAb) to human chromogranin A (CgA). Some corresponding adjacent nonmalignant mucosal tissues were also examined. Results: (I) Northern blotting: of 3 normal gastric mucosas examined, 2 (67%) had an easily detected signal for expression of CgA. Only one of 14 gastric carcinomas (7%) and one of 18 colorectal carcinomas (6%) had easily detected RNA signals. (2) Immunohistochemical staining: all non‐malignant samples of gastric and colonic mucosa contained CgA‐positive neuroendocrine (NE) cells. Two of 17 (12%) gastric adenocarcinomas, and 3 of 18 (17%) of colorectal adenocarcinomas contained CgA‐positive tumor cells. Interestingly, the positive cases detected by immunohistochemistry included both cases detected by Northern blotting. Of the 5 cases detected by immunohistochemistry, 2 gastric cancers and I rectal carcinoma contained many diffusely scattered positive cells, occurring singly or in small clusters, while 2 colorectal carcinomas contained only occasional single CgA‐positive tumor cells. In one of the positive gastric cases, a well‐differentiated adenocarcinoma arising in a tubular adenoma, both the adenomatous and the carcinomatous elements contained positively staining cells. Our specific assays for CgA indicate that (I) a NE cell component, either diffusely scattered or occasional, occurs in about 15% of gastric and colorectal tumors; (2) there is no correlation between the presence of NE cells and degree of tumor differentiation; and (3) because only a minority of the tumor cells in positive cases stain for CgA, immunohistochemistry is a more sensitive method than Northern blotting.
Laminin expression by two clones isolated from the colon carcinoma cell line lovo that differ in metastatic potential and basement‐membrane organization
Authors: Rémy L. , Lissitzky J‐C. , Daemi N. , Jacquier M. F. , Bailly M. , Martin P. M. , Bignon C. , Doré J. F. 
Published: February 2007

AbstractIn the present report we describe the characteristics of 2 clones, E2 and C5, isolated from the human colon adenocarcinoma cell line LoVo. When grafted to immunosuppressed newborn rats, these clones formed tumors that varied with regard to differentiation rate, basement‐membrane organization and lung metastatic potential. Production and distribution of laminin by E2, C5 and related tumors was studied by immunohistochemistry with an anti‐laminin monoclonal antibody 4CI2 (MAb 4CI2). In lowly metastatic E2‐derived tumors, strong regular stainings were observed which were strictly peri‐tumoral and corresponded to the basal lamina. Since the antibody interacted with human laminin (the graft) but not with rat laminin (the host), this result indicated that basementmembrane laminin was supplied mainly by tumor‐cell synthesis. In highly metastatic C5‐derived tumors, the staining obtained with MAb 4CI2 was peri‐cellular and unorganized. Laminin synthesis by E2 and C5 cells in sub‐cultures or soon after dissociation from explanted tumors was studied by metabolic labelling with 35S‐methionine under steady‐state conditions followed by immunoprecipitation and SDS‐PAGE. High‐molecular‐weight laminin comprised by disulfide‐linked A and B chains, i.e., heterotrimeric laminin, was found in cell lysates and in the secretion medium of cell lines and tumor cells. In addition, BIB2 dimers and free B chains were observed in cell lysates. Quantitatively, Iaminin expression by E2 and C5 clones or tumor cells was not significantly different. These findings suggest that basementmembrane defects in invasive clone LoVo C5 were not due to laminin under‐expression.
BI‐modal differentiation pattern in a new human neuroblastoma cell line in vitro
Authors: Matsushima Hiroshi , Bogenmann Emil 
Published: February 2007

AbstractWe have isolated a human neuroblastoma (NB) cell line, HTLA230, from the bone‐marrow aspirate of a patient with stage‐IV disease. Subcutaneous tumors after inoculation of HTLA230 cells into nude mice were composed of primitive neuroblasts which rarely contained neuro‐secretory granules. Cytogenetic studies of the cell line demonstrated 2 distinct populations of cells with common chromosomal markers. Stable sub‐clones with a differentiated or undifferentiated cell morphology were isolated, demonstrating phenotypical heterogeneity of the HTLA230 parental cell line. Treatment with retinoic acid (RA) induced extensive neurite outgrowth in the parental cell line and in phenotypically differentiated sub‐clones, but rarely in undifferentiated ones. Long‐term treatment with RA was not associated with down‐modulation of mycN‐gene expression, which could be achieved only in cultures treated additionally with aphidicolin, a DNA‐synthesis inhibitor, thus eliminating growing NB cells. A RA resistant subclone (CI‐5) was isolated from parental HTLA230 cells grown at clonal cell density. Cells originally showed a homogeneously differentiated morphology; however, flat cells (F‐cells) appeared with time and were subsequently separately propagated. Transdifferentiation of isolated F‐cells into cells with neuron‐like (N‐cell) morphology was observed. Immunohistochemical analysis demonstrated that F‐cells had lost the expression of neuronal markers, including HNK‐l and A2B5, and expressed the intermediate filament, vimentin. Furthermore, F‐cells showed high incorporation of [methyl‐3H] thymidine (3H‐TdR) by autoradiography but no mycN protein could be detected, although present in the parental cell line. These results then suggest that the isolated NB cell line and the RA‐resistant variant line represent an excellent in vitro model with which the bi‐modal differentiation pathway of NB can be analyzed on a molecular biological level.
Enhanced clearance of radiolabeled murine monoclonal antibody by a syngeneic anti‐idiotype antibody in tumor‐bearing nude mice
Authors: Sharkey Robert M. , Boerman Otto C. , Natale Ana , Pawlyk David , Monestier Marc , Losman Michele J. , Goldenberg David M. 
Published: February 2007

AbstractA syngeneic anti‐idiotype monoclonal antibody (MAb) (CM‐II) directed against an anti‐carcinoembryonic antigen (CEA) murine MAb (NP‐4) was evaluated as a second antibody (SA) to promote the rapid clearance of radiolabeled NP‐4 from the blood. Initial studies confirmed that CM‐II IgG removed 131‐NP‐4 IgG from the blood as effectively as a polyclonal donkey anti‐goat IgG removed 131I‐goat IgG. However, use of an F(ab′)2 in place of either the NP‐4 or CM‐II IgG was not as effective in removing primary radiolabeled antibody, despite the formation of high‐molecular‐weight complexes. In accordance with previous results, the timing and dose of the SA injection was critical for optimizing tumor uptake and improving tumor/non‐tumor ratios. In nude mice bearing GW‐39 human colonic tumor xenografts, a delay in the injection of CM‐II by 48 hr after injection of radiolabeled NP‐4 was optimal, since this allowed maximum tumor accretion. At a 200:1 CM‐II:NP‐4 ratio, tumor uptake was reduced, suggesting inhibition of NP‐4 binding to CEA within the tumor. Despite optimizing tumor uptake by delaying SA injection and adjusting its dose, the percentage of 131‐NP‐4 in the tumor decreased 2‐ to 3‐fold within 2 days after CM‐II injection. A similar effect was seen for 111In‐labeled NP‐4 IgG with CM‐II. Injection of excess unlabeled NP‐4 given to block CM‐II shortly after its injection failed to curtail the loss of NP‐4 from the tumor. Our results suggest that high blood levels of MAb are important for sustaining NP‐4 in the tumor. Radiation‐dose predictions derived from biodistribution studies indicate that a higher tumor dose may be delivered using the SA method than with either 131 I‐NP‐4 IgG or F(ab′)2 alone. Use of the SA method with 90Y‐labeled NP‐4 IgG, as modeled from biodistribution studies with 11In‐NP‐4 IgG, would likely be limited by liver toxicity.
No influence of beta‐carotene on smoking‐induced dna damage as reflected by sister chromatid exchanges
Authors: van Poppel G. , Kok F. J. , Duijzings P. , de Vogel N. 
Published: February 2007

AbstractThe putative cancer‐preventive potential of β‐carotene may be explained by its anti‐oxidant capacity to prevent free‐radicalinduced DNA damage. To evaluate this hypothesis, we studied the effect of 14 weeks of β‐carotene supplementation on the frequency of sister chromatid exchanges (SCE) in lymphocytes in 143 heavy smokers in a randomized, double‐blind, placebocontrolled intervention trial. Age, smoking habits and pretreatment blood levels of cotinine, β‐carotene, retinol and vitamins C and E were similar in the placebo group (n = 73) and the treatment group (n = 70). Plasma β‐carotene levels increased 13‐fold in the treatment group during intervention, whereas the other parameters remained stable in both groups. Initial SCE levels were similar in the treatment and placebo groups (5.10 ± 0.98 vs. 5.00 ± 0.99 SCE/lymphocyte). During the intervention, both groups showed an almost identical decrease, and at the end of the intervention period there was no difference in SCE levels between the treatment and the placebo groups (4.37 ± 0.38 vs. 4.24 ± 0.37 SCE/lymphocyte). This study shows no protective effect of β‐carotene on DNA damage as reflected by sister chromatid exchanges in lymphocytes. Our results thus do not yield support for a cancerpreventive mechanism of β‐carotene involving this form of DNA damage. It cannot be excluded, however, that β‐carotene prevents other forms of smoking‐induced DNA damage, affects other tissues, or is preventive in later stages of carcinogenesis.
Expression and different polarity of aminopeptidase N in normal human colonic mucosa and colonic tumors
Authors: Quaroni Andrea , Nichols Buford L. , Quaroni Elaine , Hurst Kelley , Herrera Lemuel , Weiser Milton M. , Hamilton Stanley R. 
Published: February 2007

AbstractExpression and cellular localization of brush‐border enzymes (aminopeptidase N, dipeptidylpeptidase IV, lactase, maltase) in normal human colon, colonic polyps and malignant intestinal tumors were investigated with a panel of monoclonal antibodies reacting with either native or denatured proteins. The enzymes were detected on cryostat sections by indirect immunofluorescence staining, or affinity‐purified and analyzed by gel electrophoresis and immunoblotting. Dipeptidylpeptidase IV, lactase and maltase were absent from all samples examined, while aminopeptidase N (APN) was detected at the basal membrane of the epithelial cells in most specimens of colon obtained from individuals free of intestinal tumors. In contrast, APN was frequently localized at the luminal membrane of the surface epithelium in large‐intestinal mucosa distal to tumors, adenomas and hyperplastic polyps, and from members of hereditary colon cancer syndrome families. APN was also expressed in colonic tumors, where it was present in an apical cell membrane location in 3/23 adenomas and 14/35 adenocarcinomas examined. No correlation was found between tumor‐cell invasiveness (classified by „Dukes”︁ stage) and expression or cellular location of aminopeptidase N. Histologically, all positive tumors were moderately or well differentiated. These results suggest that aminopeptidase N is normally expressed in adult human colon, but epithelial cells in the large and small intestine differ in their ways of sorting this enzyme intracellularly and eventually inserting it into different aspects of their surface membrane, a process which may be altered at an early stage of carcinogenesis.
Protective single/combined treatment with betel leaf and turmeric against methyl (acetoxymethyl) nitrosamine‐induced hamster oral carcinogenesis
Authors: Azuine Magnus A. , Bhide Sumati V. 
Published: February 2007

AbstractThe inhibitory effect of oral administration of betel‐leaf extract (BLE) and 2 of its constituents, β‐carotene and α‐tocopherol, as single agents or in combination with dietary turmeric on methyl(acetoxymethyl)nitrosamine (DMN‐OAC)‐induced oral carcinogenesis in Syrian hamsters was studied. DMN‐OAC was administered twice monthly for 6 months. The chemopreventive effect of BLE or its constituents with turmeric was determined by comparing tumor incidence observed in treated groups with that seen in control animals. The apparent sitespecific chemopreventive effect of BLE or its constituents was demonstrated by inhibition of tumor incidence, reduction of tumor burden, extension of the tumor latency period and regression of established, frank tumors. The inhibitory effect of BLE or its constituents combined with turmeric was higher than that of the individual constituents. The study suggests that BLE could be developed as a potential chemopreventive agent for human oral cancer.
Hydrolyzable tannins: Potent inhibitors of hydroperoxide production and tumor promotion in mouse skin treated with 12‐O‐tetradecanoylphorbol‐13‐acetate in vivo
Authors: Gali Hala U. , Perchellet Elisabeth M. , Klish Darren S. , Johnson Jan M. , Perchellet Jean‐Pierre 
Published: February 2007

AbstractThe anti‐oxidant and the anti‐tumor‐promotion activities of several hydrolyzable tannins (HTs), including a commercial tannic‐acid (TA) mixture, were examined in mouse skin treated with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in vivo. A single application of TPA gradually increases the hydroperoxide (HPx)‐producing activity of the epidermis, which is maximally stimulated at 3 days and returns to control levels at 9 days. Pre‐treatments with TA and ellagic acid (EA) strongly inhibit, in a dose‐dependent manner, this HPx response to TPA. Total inhibition by TA lasts for about 16 hr, beyond which it is substantially reduced but not completely lost. TA can also reduce the level of epidermal HPx when it is applied 36 hr after the tumor promoter. EA is an antioxidant 10 times more potent than TA and n‐propyl gallate (PG), which are equally effective against TPA‐induced HPx production. Gallic acid is the least effective of the HTs in inhibiting HPx formation. TA also inhibits the production of HPx induced by several structurally different tumor promoters and the greater HPx responses produced by repeated TPA treatments. When applied 20 min before each promotion treatment, twice a week for 45 weeks, several HTs inhibit the incidence and yield of papillomas and carcinomas promoted by TPA in initiated skin. Overall, TA is more effective than EA and PG in inhibiting skin‐tumor promotion by TPA, suggesting that the anti‐oxidant effects of HTs are essential but not sufficient for their anti‐tumor‐promotion activity.
A monoclonal anti‐idiotypic antibody bearing the image of an epitope specific to the human carcinoembryonic antigen
Authors: Gaida Franz‐Josef , Fenger Ursula , Wagener Christoph , Neumaier Michael 
Published: February 2007

AbstractOne concept for immune therapy of patients bearing carcinomas involves monoclonal anti‐idiotypic antibodies (Malds) to trigger the immune system of the host into a response against the tumor cells. Current theory states that so‐called internal image Malds bearing epitopes specific to a given tumor associated antigen would be most suited for that purpose. We report here the generation of syngeneic Malds generated against the murine monoclonal immunoglobulin T84.66 (Abl), which defines a single epitope on the protein moiety of the carcinoembryonic antigen (CEA). This antigenic determinant is unique to CEA, as it is absent in other members of the CEA gene family that are expressed in a variety of normal human tissues, including granulocytes. The Mald 6G6.C4 (Ab2) exhibits the immunochemical features of an internal image antibody mimicking the epitope recognized by the idiotype T84.66. In enzyme immunoassays the binding of Abl to Ab2 is completely inhibited by CEA. In addition, Mald 6G6.C4 only binds to native but not to the denatured or reduced idiotype. Immunization of rabbits with F(ab′)2‐fragments of 6G6.C4 results in antisera (Ab3) that show specificity to CEA in both binding and inhibition enzyme immunoassays as well as in Western blots. Finally, Ab3 did not detect NCA, a major CEA‐related glycoprotein in Western blots, either in a purified form or in a crude tumor extract, indicating a high specificity of the anti‐anti‐idiotypic response. In summary, these immunochemical data show that the monoclonal anti‐idiotype 6G6.C4 can functionally mimic a CEA specific epitope in rabbits and may do so in humans. Therefore, this antibody may have a clinical potential as a network antigen for active immune therapy in patients suffering from CEA positive carcinomas.
Treatment of l1210 murine leukemia with liposome‐incorporated N4‐hexadecyl‐1‐β‐D‐arabinofuranosyl cytosine
Authors: Schwendener R. A. , Schott H. 
Published: February 2007

AbstractN4‐alkyl‐1‐β‐D‐arabinofuranosyl cytosines as lipophilic derivatives of the widely used anti‐tumor drug 1 ‐β‐D‐arabinofurano sylcytosine (ara‐C) were synthesized and incorporated into unilamellar liposomes. The resulting preparations yielded stable unilamellar liposomes with diameters ranging between 40 and 70 nm. The liposomal derivatives exhibited an increased antitumor effect against the murine L1210 lymphoid leukemia at optimal molar concentrations which were 16 times lower than those previously reported for free ara‐C. The N4‐alkyl‐ara‐C derivatives with alkyl chains containing 14–16 C‐atoms were highly effective against L1 210 leukemia whereas shorter chains showed no cytostatic effects. The increased resistance to hydrolysis of the N4‐alkyl‐ara‐C derivatives and the improved anti‐tumor effect of the liposomal N4‐hexadecyl‐ara‐C preparation compared to other known N4‐acyl‐ara‐C prodrugs, together with the possibility of preparing large volumes of stable and sterile liposomes, hold out the prospect of more effective chemotherapy for leukemias.
The presence of a concomitant bulky tumor can decrease the uptake and therapeutic efficacy of radiolabeled antibodies in small tumors
Authors: Boerman O. C. , Sharkey R. M. , Blumenthal R. D. , Aninipot R. L. , Goldenberg D. M. 
Published: February 2007

AbstractWe describe the effects that a concomitant large tumor mass can exert on the therapeutic efficacy of radioimmunotherapy against small tumors, using the nude mouse/GW‐39 human colonic cancer model. The tumor uptake 7 days p.i. of i.v.injected 131l‐labeled anti‐CEA MAb (NP‐4) and anti‐CSAp MAb (Mu‐9) in small (<0.2 g) s.c. GW‐39 tumors was approximately 3‐fold lower in animals with a concomitant large (> 1.0 g) GW‐39 tumor than in the absence of a large tumor. An inverse correlation between the mass of the tumor burden and the 131l levels in the blood was observed, indicating that a large tumor mass may act as a sink for the injected radiolabeled antibody. Increasing antibody protein dose did not reverse the reduced uptake in the small s.c. tumors. The therapeutic efficacy of a single 0.25‐mCi injection of 131l‐labeled anti‐CSAp MAb Mu‐9 towards intrapulmonary GW‐39 metastases was tested in nude mice bearing either small or large GW‐39 s.c. tumors. Over 80% of the animals with small s.c. GW‐39 tumors survived 18 weeks after tumor transplantation, whereas less than 20% of the animals bearing large s.c. tumors survived past 13 weeks. Dosimetric calculations, based on biodistribution data over time, indicated that the presence of a large s.c. tumor mass may have decreased the radiation dose to the intrapulmonary tumors almost two‐fold. However, the radiation dose to the blood was also decreased in the animals with the large tumor burden. Therefore, the animals with larger tumor burden may also have been able to sustain higher doses of the radioantibody. The presence of a large tumor mass can thus affect the biodistribution and therapeutic efficacy of radioiodinated antibodies. We suggest that bulky tumors can adsorb a considerable amount of the injected dose, thereby reducing the total amount of MAb available for binding to the smaller tumors.
Hepatitis B Virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: A Case‐Control study in Fukuoka, Japan
Authors: Tanaka Keitaro , Hirohata Tomio , Takeshita Setsuko , Hirohata Itsuyo , Koga Shunichi , Sugimachi Keizo , Kanematsu Takashi , Ohryohji Fumitake , Ishlbash Hiromi 
Published: February 2007

AbstractThe roles of the hepatitis B virus (HBV), cigarette smoking and alcohol consumption in the etiology of hepatocellular carcinoma (HCC) were examined in a case‐control study involving 204 patients with HCC and 410 control subjects in Fukuoka prefecture, where HCC risk is among the highest in Japan. Information on smoking and drinking habits was obtained by a detailed interview survey, and the results were analyzed in conjunction with serum hepatitis B surface antigen (HBsAg) status after adjustment for sex, age and other possible confounding factors. Individuals positive for serum HBsAg showed a relative risk (RR) for HCC of 13.8 (95% confidence interval, CI 5.9 to 32.5), whereas heavy drinkers experienced about a 2‐fold risk increase compared with non‐drinkers. Light or moderate drinkers, however, demonstrated RRs near the unity. Some risk excess was observed among ex‐smokers (RR = 1.5,95% CI 0.8 to 2.8) and current smokers (RR = 1.5, 0.8 to 2.7) compared with non‐smokers, but without evidence for a dose‐response relationship in terms of pack‐years. Analysis among HBsAg‐negative subjects revealed similar non‐significant association with smoking, and there was no clear interaction between alcohol and cigarette consumption on HCC risk. Other significant risk factors included positive histories of blood transfusion (RR = 3.7,2.2 to 6.3) and familial liver disease (RR = 2.6, 1.6 to 4.2). Attributable risk calculations suggest that chronic HBV infection and heavy drinking may account for 17% and 13% of HCC occurrence, respectively, in this high risk area. The association of cigarette smoking with HCC was not evident in our study.
Frequent expression of the tumor antigen cak1 in squamous‐cell carcinomas
Authors: Chang Kai , Pastan Ira , Willngham Mark C. 
Published: February 2007

AbstractKI is a murine monoclonal antibody (MAb) derived from a hybridoma generated by the fusion of splenocytes of BALB/c mice immunized with a human ovarian tumor cell line, OVCAR‐3. This antibody reacts strongly with epithelial ovarian tumors and mesotheliomas. The antigen recognized by MAb Kl, designated CAKI, has recently been characterized as a 40‐kDa protein probably anchored to the cell surface by glycosyl‐phosphatidyli‐nositol. Using immunoperoxidase histochemical methods, we examined 37 squamous‐cell carcinoma (SqCC) samples from cervix, lung, esophagus and other origins, and 12 normal squamous epithelia of the cervix and esophagus for their reactivity with MAb KI. Of the SqCC specimens, 81% showed Kl reactivity with variable intensity, but none of 12 normal tissue samples of squamous epithelia did so. Two patterns of CAKI expression in tumor samples were found, i.e., a heterogeneous pattern with strong intensity, and a homogeneous pattern with weak intensity. Three carcinomas in situ of the larynx, vulva and esophagus were moderately positive with KI, suggesting that CAKI antigen may occur in the early stage of carcinogenesis of SqCC. The expression of CAKI was also compared with expression of CAI25, HER‐2/neu, p53 and P‐glycoprotein, and MAb KI was found to react most consistently with SqCC. Since KI reacts with a majority of cervical and esophageal carcinomas but has no detectable reactivity in normal epithelia of the cervix uteri and esophagus, MAb KI could be of value as a reagent to help distinguish between normal and neoplastic cells on sections as well as in cytological samples.