bluuebunny/crossref_metadata_2025_split huggingface dataset:
Confluence‐dependent resistance in human colon cancer cells: Role of reduced drug accumulation and low intrinsic chemosensitivity of resting cells
Authors: Dimanche‐Boitrel Marie‐ThéRéSe , Pelletier Hélène , Genne Philippe , Petit Jean‐Michel , Grimellec Christian Le , Canal Pierre , Ardiet Claude , Bastian Gérard , Chauffert Bruno 
Published: February 2007

AbstractIn vitro sensitivity of HT29 human colon cancer cells to doxorubicin (DXR), vincristine (VCR), etoposide (VP16), cisplatin (CDDP), melphalan (L‐PAM) and 5‐fluorouracil (5FU) was markedly reduced when cell‐culture density increased. For some drugs, confluence‐dependent resistance (CDR) was partly due to decreased intracellular drug accumulation; the ratio of mean intracellular drug content of non confluent to confluent cells (NC/C) was 2.5 for DXR, 4.1 for VCR and 7.4 for VP16. Altered drug penetration with confluence could be related to decrease of plasma membrane fluidity as measured by the fluorescence polarization method. Reduction of drug intracellular accumulation was nil or weak for L‐PAM (NC/C = 1.0), CDDP (NC/C = 1.2) and 5 FU (NC/C = 1.8). Even if drug concentration was adjusted in culture medium to produce similar intracellular drug content in confluent and non confluent cells, higher intrinsic resistance of confluent cells was still evidenced for DXR and VP16 but not for VCR, the only agent without direct interaction with DNA. DXR‐ and VP16‐induced DNA breakage was also less important in confluent than in non‐confluent cells. CDR appeared closely related to an increased proportion of non‐cycling cells at confluence, as demonstrated by flow cytometry, expression of nuclear antigen recognized by Ki67 MAb and expression of topoisomerase II. CDR is probably a major factor in the poor sensitivity of colorectal adenocarcinomas to chemotherapy.
Over‐expression of p53 nuclear oncoprotein in colorectal adenomas
Authors: Pignatelli Massimo , Stamp Gordon W. H. , Kafiri Georgia , Lane David , Bodmer Walter F. 
Published: February 2007

Abstractp53 is a nuclear phosphoprotein which controls normal cell growth. Normal p53 protein is undetectable by standard immunohistochemical staining and the over‐expression found in neoplastic cells correlates with the presence of point mutations of evolutionary conserved regions of the p53 gene. We examined the expression of p53 protein in a series of 36 colorectal adenomas (13 tubular, 17 tubulovillous, 6 villous) showing different degrees of dysplasia (11 mild, 19 moderate, 6 severe), 11 moderately differentíated adenocarcinomas (6 Duke's A, 4 Duke's B, 1 Duke's C) and 5 metaplastic polyps using the polyclonal antibody CM1 which recognises p53 protein in conventionally fixed and processed histological material. We found that 15 out of 36 colorectal adenomas showed p53 immunoreactivity, although in 4 positive cases (26%) the staining was very focal (<0.1% positive cells). More than 80% of severely dysplastic adenomas showed strong p53 immunoreactivity and this over‐expression was correlated with increased cell proliferative rate as detected by the proliferating‐cell‐nuclear‐antigen (PCNA) staining. p53 nuclear staining was also seen in 8 out of 11 (65%) colorectal adenocarcinomas as previously shown. Our data suggest that the p53 gene mutation, with the subsequent over‐expression of the protein, occurs in colorectal adenomas and may therefore be a fundamental genetic event underlying the dysplasia and loss of proliferative control that are characteristic of adenomas with malignant potential.
Effect of a single infusion of alendronate in malignant hypercalcaemia: Dose dependency and comparison with clodronate
Authors: Rizzoli R. , Buchs B. , Bonjour J.‐P. 
Published: February 2007

AbstractAmong aminohydroxybisphosphonate derivatives, atendronate (3‐amino‐1‐hydroxybutylidene‐1, 1‐bisphosphonate) has proved efficacious in diseases with increased bone resorption. However, the effective dose in the treatment of malignant hypercalcaemia is not clearly established. In 2 randomized studies, we investigated the effects of alendronate and of clodronate (dichloromethylene bisphosphonate) given as a single infusion in 82 rehydrated patients with malignant hypercalcaemia. Various doses of alendronate or clodronate soon produced a significant fall in plasma calcium (Ca), accompanied by a dose‐dependent decrease in the fasting urinary Ca/creatinine ratio, taken as a reflection of bone resorption. During the next 5 days, plasma Ca and fasting urinary Ca/creatinine ratio were lower in the group treated with alendronate than in the clodronate group. The renal handling of Ca was similar in both groups. Because of relapsing hypercalcaemia, some patients received an infusion of alendronate approximately 2 weeks after the first infusion; this normalized the urinary Ca/creatinine ratio in 44% of the cases at day 3. At that time, the plasma Ca was below 2.70 mmol/l in 33%. Our results indicate that alendronate decreased bone resorption and calcaemia in cancer patients in a dose‐dependent manner.
Autoradiographic and flow‐cytometric assessment of cell proliferation in primary colorectal cancer: Relationship to dna ploidy and clinico‐pathological features
Authors: Costa A. , Faranda A. , Scalmati A. , Quagliuolo V. , Colella G. , De Leon M. Ponz , Silvestrini R. 
Published: February 2007

AbstractTwo cell‐kinetic parameters, the [3H]thymidine‐labeling index [3H]dT LI and the flow‐cytometric S‐phase cell fraction (FCM‐S), and DNA ploidy were determined for a prospective series of 110 primary colorectal cancers. Aneuploidy was observed in 66% of tumors and more than one aneuploid peak was present in 12%. The frequency of aneuploid tumors was higher in rectal (80%) and left‐colon (70%) cancers than in right‐colon cancers (51%), and multiple aneuploid clones were detected more frequently in men than in women (p = 0.03) and more frequently in advanced Dukes' D‐stage patients (p = 0.08). The median [ H]dT LI value (17.4%) was similar to the FCM‐S value determined by a planimetric model (16.2%) and somewhat higher than the FMC‐S value obtained by an optimization procedure (11.2%). However, there was no significant relationship between the [3H]dT LI value and either FCM‐S value for individual tumors. Moreover, FCM‐S values were higher in aneuploid than in diploid tumors, whereas [3H]dT LI values were independent of DNA‐ploidy status; [3H]dT LI and FCM‐S were also related differently to some clinical and pathological features such as tumor site and histology. These findings suggest different biological meanings for these 2 cell‐kinetic parameters, which should not be used interchangeably.
Protein kinase C activity and expression in normal and adenomatous human pituitaries
Authors: Alvaro V. , Touraine P. H. , Vozari R. Raisman , Bai‐Grewer F. , Birman P. , Joubert (Bression) D. 
Published: February 2007

AbstractProtein kinase C (PKC) activity and expression were measured in 54 adenomas (prolactin (PRL)‐, growth hormone (GH)‐and non‐secreting), I of them obtained from a patient treated with the dopamine agonist bromocriptine and 2 from patients treated with the somatostatin analog octreotide. They were also measured in normal human and rat pituitaries. Total PKC activity was measured by incorporation of 32P into histones, and PKC expression by dot blot immunoquantification using purified PKC as a standard. Both enzyme activity and expression were higher in adenomatous pituitaries than in normal human or rat pituitaries. PKC expression in GH‐secreting and non‐secreting tumors was significantly higher than that in PRL‐secreting tumors. Furthermore, it was significantly higher in invasive tumors than in non‐invasive tumors. In the 3 adenomas which were obtained from patients treated with bromocriptine or octreotide and which were used for PKC‐activity measurement, particulate‐ and soluble‐PKC activities were significantly lower than those measured in non‐treated adenomas.
Differential screening of a human pancreatic adenocarcinoma λgt11 expression library has identified increased transcription of elongation factor ef‐1α in tumour cells
Authors: Grant Anne G. , Flomen Rachel M. , Tizard Mark L. V. , Grant David A. W. 
Published: February 2007

AbstractA human pancreatic adenocarcinoma λgt11 expression library was differentially screened with mRNA derived from normal and cancerous pancreatic tissues. Five clones preferentially hybridized with pancreatic adenocarcinoma mRNA. cDNA inserts from 4 of these clones were amplified by PCR, labelled with α32P and used in Northern blot analysis against mRNA prepared from a variety of tumour and normal tissues. λGER‐4 identified a pancreas‐associated mRNA (> 10 kb) with no homology with known sequences at either the nucleic or amino‐acid level. λGER‐2 identified a 1.7‐kb mRNA transcript that was over‐expressed in mRNA prepared from pancreas, colon, breast, lung and gastric tumours relative to normal tissues. Sequence analysis and restriction‐enzyme mapping showed that this clone was completely homologous with the active form of human elongation factor EF‐1α. This high level of EF‐1α‐mRNA expression in tumour tissues lends support to the increasing evidence that EF‐1α is an important regulator of the cell cycle.
Differential cytostatic activity of monocyte‐derived cytokines against human melanoma cells
Authors: Te Velde Anje A. , Kemenade Elly V. D. Wiel‐V. , Figdor Carl G. 
Published: February 2007

AbstractWe investigated the capacity of 3 major cytokines secreted by activated monocytes, IL‐1β, TNFα and IL‐6, to inhibit growth of melanoma tumor cells. Using neutralizing antibodies against IL‐1β, TNFα and IL‐6, we observed that the cytostatic activity against A375 melanoma cells is largely due to the presence of IL‐6 in culture supernatants of monocytes stimulated with LPS. A375 cells appeared to be extremely sensitive to monocyte‐derived cytokines, since in addition to rIL‐6 also rIL‐1β and rTNFα displayed cytostatic activity against A375 cells. We observed additive or synergistic cytostatic effects upon use of combinations of these cytokines. When 7 other melanoma cell lines and short‐term melanoma cultures were tested and compared with A375, a major difference in their sensitivity to monocyte‐derived cytokines were observed. Although 7 out of 8 melanoma cell lines were sensitive to culture supernatants of monocytes stimulated with LPS, significant differences were found when recombinant cytokines were used. The widely used A375 was the only melanoma cell line sensitive to rIL‐1β, rTNFα and rIL‐6. The growth of none of the other 7 melanoma cell cultures was significantly affected by rIL‐1β. Seven out of 8 melanoma cell cultures were sensitive to rTNFα and 3 out of 8 to rIL‐6. The results of our study indicate that the sensitivity of melanoma cell cultures for different monocyte‐derived cytokines is highly variable, and that it is questionable whether the A375 melanoma cell line, sensitive to rIL‐1β, rTNFα and rIL‐6, is representative for melanoma.
Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice
Authors: Kim Ryungsa , Hirabayashi Naoki , Nishiyama Masahiko , Jinushi Kazuto , Toge Tetsuya , Okada Kosuke 
Published: February 2007

AbstractTopoisomerase (topo) I and II are nuclear enzymes which are novel targets of cancer chemotherapy. A new camptothecin (CRT) analog, 7‐ethyl‐10‐[4‐(I‐piperidino)‐I‐piperidino]carbonyl‐oxy‐CPT (CRT‐11), is a topo‐I inhibitor with a higher activity and less toxicity than CPT. To investigate topo‐I and‐II‐targeting chemotherapy in an in vivo model, we studied the effect of sequential or co‐treatment using CPT‐11 and adriamycin (ADR) a topo‐II inhibitor, in 6 human tumor xenografts (2 esophageal, 2 gastric and 2 colon tumor lines). In sequential treatment, adriamycin was administered i.v. 24 hr after CPT‐11 treatment, and no antagonistic effect of this treatment schedule was observed. ADR cytotoxicity was potentiated significantly by CPT‐11 pretreatment in the case of 2 esophageal and 2 gastric tumor lines and I colon tumor line. On the other hand, co‐treatment abolished the sensitivity to CPT‐11 and ADR in all 6 tumor lines. Moreover, CPT‐11 did not significantly enhance the cytotoxicity of other agents tested, including mitomycin C (MMC) and cisplatin (CDDP). Flow cytometry and dot‐blot analyses showed that CPT‐11 pretreatment induced an increase in the S‐phase cell population with an increase of topo‐II mRNA expression after 24 and 48 hr, respectively, in the esophageal and colon tumor lines. These results suggest that CPT‐11 can modulate topo‐II levels to enhance the effect of topo‐II inhibitors in some human tumors, and this suggests a new clinical method of topo‐I and‐II targeting chemotherapy for human solid tumors.
Effect of TGF‐β1 on the ebv‐induced transformation of human lymphocyte cultures
Authors: Altiok Aysin , Bejarano Maria Teresa , Klein George , Klein Eva 
Published: February 2007

AbstractWe tested the effect of TGF‐β1 on the EBV‐induced activation and immortalization of human B lymphocytes. In lymphocyte cultures of EBV‐seropositive individuals, T cells can inhibit the EBV‐induced transformation of B cells. We found that in the presence of TGF‐β1 the transformation was more efficient, due to the inhibition of this function. TGF‐β1 inhibited the EBV‐induced proliferation of purified B‐cell cultures. Its effect was strongest when added at the beginning of the culture. Added later, the inhibition gradually decreased and was lost by the 4th day. After 10 to 14 days, in the cultures initiated with TGF‐β1, the number of cells was higher and they formed larger aggregates as compared with control cultures. Thus, TGF‐β1 modifies EBV‐induced transformation in a complex way. It inhibits the activation of B cells but does not affect those already activated. Once they acquire the immortalized state, the B cells are even stimulated by TGF‐β1.
Expression of the tumor‐associated mucin MUCI in an ovarian tumor cell line
Authors: Stern Linda , Palatsides Manuela , De Kretser Theonne , Ford Miriam 
Published: February 2007

AbstractEpithelial sialomucins constitute a family of high‐molecular‐weight glycoproteins associated with epithelial cell surfaces. Aberrant expression of these molecules has been observed in certain types of human epithelial tumors. Members of the MUCI family of mucins isolated from different tissue types have been shown to differ in biochemical properties and in immunological reactivity. The polymerase chain reaction (PCR) has been used in a study of the MUCI mRNA expressed in ovarian tumor cells. The intron/exon structure of the ovarian mucin gene has been examined, the nucleotide sequence of regions of the cDNA 5' and 3' to a central highly repetitive region of the molecule determined and genomic clones for this mucin from the ovarian tumor cell line COLO316 have been isolated and analyzed. The results are compared with the nucleotide sequence data obtained by others for MUCI cDNA in breast and pancreatic cell lines. With a single nucleotide exception, the splicing pattern and nucleotide sequence obtained from MUCI mRNA in the ovarian cell line is the same as that of the mRNA found in breast and pancreatic cell lines. However, it appears that the use of alternate splice acceptors for intron I in the ovarian cell line studied here is independent of the specific sequence variation thought to determine splicing of MUCI in breast tumor cells.
Basic fibroblast growth factor induces proliferation of a rat pancreatic cancer cell line. Inhibition by somatostatin
Authors: Bensaïd M. , Tahiri‐Jouti N. , Cambillau C. , Viguerie N. , Colas B. , Vidal C. , Tauber J. P. , Estève J. P. , Susini C. , Vaysse N. 
Published: February 2007

AbstractAR4–2J, a rat pancreatic acinar‐tumor cell line, was used to investigate long‐term effects of basic fibroblast growth factor (bFGF) and somatostatin on pancreatic cancer cells. We observed that bFGF stimulated cell proliferation when cells were cultured in serum‐free medium. The effect was dose‐dependent with half‐maximal and maximal effects at 25 pM and I nM bFGF, respectively. The somatostatin analog SMS 201–995 (SMS) decreased the growth‐promoting effect of bFGF. The maximal effect was observed at I nM SMS and the half‐maximal effect at 20 pM SMS. Characterization of bFGF receptor‐binding properties with [125I]bFGF revealed that AR4–2J cells exhibited 2 classes of bFGF binding site with respective KD values of 47 pM and 3 nM and binding capacities of 14 fmol and 0.9 pmol/106 cells. High‐affinity receptors correlated with bFGF stimulation of AR4–2J cell growth, suggesting that the effects of bFGF are receptor‐mediated.
Human C‐ERBB‐2 proto‐oncogene product as a target for bispecific‐antibody‐directed adoptive tumor immunotherapy
Authors: Nishimura Takashi , Nakamura Yoshihiko , Tsukamoto Hideo , Takeuchi Yasuhiro , Tokuda Yutaka , Iwasawa Megumi , Yamamoto Tadashi , Masuko Takashi , Hashimoto Yoshiyuki , Habu Sonoko 
Published: February 2007

AbstractTo develop an efficient strategy for the targeting of anti‐tumor effector cells, we prepared bispecific antibody (BsAb) containing anti‐CD3 and an anti‐c‐erbB‐2 proto‐oncogene product. The prepared BsAb specifically reacts with both c‐erbB‐2‐positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from peripheral‐blood mononuclear cells by activation with immobilized anti‐CD3 monoclonal antibody (MAb) plus IL‐2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb caused the induction of specific cytotoxicity against c‐erbB‐2‐positive tumor cells. CD4+ helper/killer cells also produced significant amounts of IL‐2 during co‐culture with c‐erbB‐2‐positive tumor cells in the presence of the BsAb. Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong in vivo anti‐tumor effect against c‐erbB‐2 transfectant or human colon‐cancer cells implanted in nude mice. Our results strongly suggest that the c‐erbB‐2 proto‐oncogene product on human tumor cells may be a good target for BsAb‐directed adoptive tumor immunotherapy.
TGF‐β stimulation of endometrial and breast‐cancer cell growth
Authors: Croxtall J. D. , Jamil A. , Ayub M. , Colletta A. A. , White J. O. 
Published: February 2007

AbstractGrowth of the human endometrial carcinoma Ishikawa cell line was stimulated by transforming growth factor‐β1 when cultured in serum‐containing and chemically defined culture medium. This response was not unique to endometrial carcinoma cells, as the breast‐cancer cell line, T47‐D, was similarly stimulated by TGF‐β1. TGF‐β1 stimulated growth of MCF‐7 breast‐cancer cells in chemically defined medium but inhibited growth of this cell fine in serum‐containing medium. The data provide a demonstration of a positive growth response to TGF‐β1 in oestrogen‐receptor‐positive cells and do not support the hypothesis that this growth factor is simply a negative growth regulator in epithelial‐cancer cell lines.
Enhancement by bombesin of colon carcinogenesis and metastasis induced by azoxymethane in wistar rats
Authors: Iishi Hiroyasu , Tatsuta Masaharu , Baba Miyako , Yamamoto Reiko , Taniguchi Haruo 
Published: February 2007

AbstractThe effects of bombesin on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on their metastases to the peritoneum and/or lymph nodes, were investigated in Wistar rats. Rats received weekly s.c. injections of AOM for 10 weeks, and s.c. injections of bombesin in depot form every other day until the end of the experiment in week 30. Administration of bombesin significantly increased the incidence of colon tumors in week 30. It had no influence on the histological features or depths of involvement of colon adenocarcinomas, but significantly increased the incidence of cancer metastasis to the peritoneum and/or lymph nodes. It also caused a significant increase in the labeling index of the colon epithelial cells. Our findings indicate that bombesin enhances the development and metastasis of colon tumors, and that this effect may be related to its effect in increasing proliferation of epithelial cells of the colon.
Basal‐cell carcinoma in temperate and tropical Australia
Authors: Czarnecki D. , Collins N. , Meehan C. , O'Brien T. , Leahy S. , Nash C. 
Published: February 2007

AbstractThe clinical features of patients with basal‐cell carcinoma (BCC) living in temperate and tropical Australia were studied. In the temperate zone the patients were considerably older on average, men outnumbered women and there were differences between the sexes in the site of the prevalent BCC. In the tropics the patients were significantly younger on average, the male‐to‐female ratio approached unity and there were no differences between the sexes with regard to the site of the BCC.
Tumorigenicity, mucin production and AM‐3 epitope expression in clones selected from the HT‐29 colon carcinoma cell line
Authors: Hanski C. , Stolze B. , Riecken E. G. 
Published: February 2007

AbstractTwo mucin‐producing cell clones (16.2 and 12.2) and a mucin‐deficient clone (15.2) were selected from the established human adenocarcinoma cell line HT‐29 by limiting dilution and Alcian blue staining. The amounts of the mucin antigen detectable on the cell surface with the monoclonal antibody (MAb) AM‐3 decreased in the order HT‐29 > 16.2 > 12.2 > 15.2 = 0. The binding avidity of AM‐3 antibody to cells as well as to mucin extracts from each cell line decreased in the same order, indicating that the epitope density on the cell‐bound mucins was highest in HT‐29 and lowest in 12.2 cells. The parental line and the mucin‐producing cell clones 16.2 and 12.2 showed no contact inhibition and grew as aggregates, while the 15.2 cells were well spread and formed a regular monolayer. The mucin‐producing cell lines injected into nude mice yielded solid tumors with different growth rates (HT‐29 > 16.2 > 12.2), while the 15.2 cell clone was not tumorigenic at all. The relative amounts of total mucin‐bound hexoses and of the mucin epitope AM‐3 decreased in the xenografts in the order HT‐29 > 16.2 > 12.2. The present system is suitable for investigating the role of mucins in growth of colon carcinoma cells and indicates that increased tumorigenicity in nude mice coincides with the increase in total mucin expression and the expression of the AM‐3 mucin epitope in tumor tissue.
Identification of high‐density lipoprotein in serum to determine anti‐cancer efficacy of doxorubicin in HeLa cells
Authors: Yung Benjamin Yat‐Ming , Bor Amy Meei‐Shuu 
Published: February 2007

AbstractThe cytotoxic effects of doxorubicin (DOX) and daunorubicin (DAU) on HeLa cells cultured under different serum conditions were analyzed by the “nucleophosmin translocation” assay using immunofluorescence. Bright nucleolar fluorescence was observed in untreated cells. A shift from nucleolar to nuclear fluorescence was observed with increasing doses of DOX or DAU, with longer incubation times. A lesser degree of nucleophosmin translocation from nucleoli to nucleoplasm was observed in serum‐deprived cells under the same DOX or DAU treatment. These results correlated well with those of cell‐growth‐reversibility and colony‐formation studies, showing decreased inhibitory effects of growth on cells cultured in medium without serum. Furthermore, cells cultured in medium supplemented with the lipoprotein‐free serum responded to DOX in a similar way to cells cultured without serum. High‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) were then added to the lipoprotein‐free serum. Cells cultured in medium with the HDL‐supplemented, serum showed increased sensitivity to DOX. Inhibition of cell growth and colony formation was observed in such HDL‐supplemented cells upon DOX treatment (30 min). LDL, on the other hand, did not show an increase in the anti‐cancer response. These results suggested that the variation in response of cells to DOX anti‐cancer treatment under different growth conditions may be due to their varied concentrations of HDL. “Nucleophosmin translocation”, which is useful for monitoring and ensuring the efficacy of the drug during anti‐cancer treatment, provides an improved potential for successful chemotherapy.