bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granulocytic colony‐stimulating factor (G‐CSF) does not induce differentiation of WEHI3B(D+) cells but is required for the survival of the mature progeny
Authors: Böhmer Ralph M. , Burgess Antony W. 
Published: February 2007

AbstractIt has been reported previously that cells of the murine myelomonocytic leukaemia cell line WEHI3B(D+) can be induced to differentiate into mature monocytes by incubation with post‐endotoxin serum (ES), granulocyte‐colony‐stimulating factor (G‐CSF) or actinomycin D (AMD). We have investigated the kinetics of the differentiation process in suspension cultures, using growth curves and morphological markers to analyze proliferation and differentiation. At low cell densities (<105/ml) neither ES nor G‐CSF changed the rate of WEHI3B(D+) proliferation; nor did these reagents induce the differentiation of WEHI3B(D+). In contrast, AMD caused growth arrest and initiated cell maturation, which was followed by cell death. The time course of maturation depended on AMD concentration. The addition of either ES or G‐CSF at the time of AMD exposure or at times up to 20 hr after the beginning of AMD exposure resulted in a delay of cell death for up to 3 days and in an accumulation of mature monocytes. The kinetics of AMD‐induced maturation were not affected by the time of ES or G‐CSF addition. We conclude that neither ES nor G‐CSF induce the differentiation of WEHI3B(D+) cells directly, but that their presence permits the survival of mature cells produced from WEHI3B(D+) as a result of a shortrange autocrine‐induced differentiation.
Induction of tumor suppression and delayed‐type footpad reaction by transfer of lymphocytes sensitized to a xenogenized tumor variant
Authors: Bianchi R. , Romani L. , Puccetti P. , Fioretti M. C. 
Published: February 2007

AbstractSplenocytes immune to a highly immunogenic (“xenoge‐nized”, L5178Y/DTIC) variant of a murine lymphoma exert anti‐parental‐tumor activity in a systemic adoptive transfer system, the effect being apparently associated with the Lyt‐2− fraction of the lymphocyte population. During investigation of the mechanisms of this protection, we found that the L5178Y/DTIC tumor‐immune lymphocytes exhibited an appreciable anti‐L5178Y delayed‐type hypersensitivity (DTH) response. Enrichment of those lymphocytes in L3T4+ cells significantly enhanced the protective effect as well as the DTH reaction, whereas the use of an anti‐L3T4 but not anti‐Lyt‐2 reagent blocked both activities. In vitro, lymphocyte proliferation against L5178Y cells occurred and was apparently associated with the Lyt‐2− fraction of a population of L5178Y/DTIC immune splenocytes.
Serotherapy of cancer: Cellular changes in primary rat mammary carcinomas after infusion of syngeneic sera absorbed with protein a‐sepharose
Authors: Glenn Gladys M. , Szende Bela , Yano Takahiko , Zbar Berton , Borsos Tibor 
Published: February 2007

AbstractSerotherapy and plasma therapy have proved to be effective in the treatment of diverse neoplasms. The mechanisms of the tumoricidal or growth‐inhibitory effects are unknown. We previously reported that activation of the alternative pathway of complement in absorbed sera correlated with the presence of anti‐tumor activity. Complement components generated during absorption may serve as the initial mediators of cytotoxicity; for example, C5a may function in its role as a chemo‐attractant. To further investigate the anti‐tumor mechanisms, we undertook a series of sequential histological studies of in vivo changes in tumors following i.v. serotherapy. We found diffuse inflammatory cellular infiltrates in the interstitial compartments of primary mammary carcinomas of rats within 3–4 hr of administration of protein A‐Sepharose absorbed syngeneic serum. The number of inflammatory cells was significantly higher in tumors from treated rats: total infiltrating cells (p = 0.002), eosinophils (p = 0.001), neutrophils (p = 0.001), macrophages (p = 0.001), lymphocytes (p = 0.004) and plasma cells (p = 0.001). Also, the mitotic index of tumor cells was significantly lower 4 hr after serotherapy when compared with that of untreated rat tumor cells. C3 in tumor tissue was decreased at 4 hr following serotherapy. Fibrosis was present in tumor nodules with retarded growth 5 weeks after the start of serotherapy. Localization of the infiltrating cells to tumor interstitial compartments prevents direct contact between inflammatory cells and neoplastic cells, making it unlikely that direct cell‐cell killing occurs. Indirect cell killing within the tumor bed apparently occurs through several mechanisms involving interactions between serotherapy‐initiated humoral mediators and inflammatory cells. The resulting anti‐tumor effects include microvascular injury leading to localized ischemia, tumor infarction, and fibroblastic reactions obstructing tumor invasion and growth.
Phenotypic resistance to methotrexate and N‐phosphonacetyl L‐aspartate is induced by treatment with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)
Authors: Kinsella Anne R. , Fox Margaret 
Published: February 2007

AbstractThree different 3T6 mouse fibroblast cell clones with intrinsically different sensitivities to methotrexate (MTX) have been isolated from an originally heterogeneous population. When these 3 different clones were exposed to MTX in the presence of the tumour promoter 12‐O‐tetradecanoylphor‐bol‐13‐acetate (TPA) the degree of enhancement of recovery of methotrexate resistant (MTXR) colonies was greatest in the most sensitive clone. MTXR colonies isolated and cultured in the presence and absence of MTX and TPA were analysed for dihydrofolic acid reductase (dhfr) levels by flow cytometry after binding of fluorescent methotrexate. None of the 58 clones showed major changes in dhfr levels. Dot‐blot analysis of 12 clones indicated no increases in dhfr gene copy number or mRNA levels consistent with gene amplification. Southern analysis of 6 further clones indicated that only I clone isolated by multi‐step selection had amplified dhfr sequences. TPA‐enhanced mouse 3T6 N‐phosphonacetyl‐L‐aspartate (PALA)‐resistant colony recovery and mouse 3T3 MTXR colony recovery were also shown, by dot‐blot analysis, not to be due to gene amplification. The data indicate that TPA can have a profound effect on drug‐resistant colony recovery by mechanisms other than induction of gene amplification.
Paracrine influence of human breast stromal fibroblasts on breast epithelial cells: Secretion of a polypeptide which stimulates reductive 17β‐oestradiol dehydrogenase activity
Authors: Adams Eric F. , Newton C. J. , Tait G. H. , Braunsberg H. , Reed M. J. , James V. H. T. 
Published: February 2007

AbstractWe have previously shown that a stroma‐associated paracrine influence may occur in the human breast. In particular, human breast fibroblasts secrete a factor which stimulates reductive 17ß‐oestradiol dehydrogenase (HSD) activity, thereby regulating tissue concentrations of 17ß‐oestradiol. We report here the results of experiments designed to establish the nature of the enzyme activity stimulating factor. In vitro cell culture techniques were used, in which human breast fibroblast‐conditioned medium was used to grow the human breast cancer cell line, MCF‐7, for 6 days, after which the reductive HSD activity of the monolayers was assessed. The fibroblastic reductive HSD stimulating factor was found to be a trypsinsensitive polypeptide. The polypeptide eluted from a Sephadex G‐75 column as a peak corresponding to a molecular weight of about 50 kDa. The polypeptide exerts its effects by altering the Vmax of 2 of the cytosolic forms of HSD within MCF‐7 cells. This is achieved by a protein‐synthesis‐dependent but calmodulin‐independent mechanism. These results provide further evidence of a paracrine effect by stromal tissue within the human breast and have important implications with respect to the aetiology and treatment of breast cancer.
Immunization against the polyoma tumor‐specific transplantation antigen (TSTA) with polyoma T‐antigens
Authors: Ramqvist T. , Pallas D. O. , Deanda J. , Ährlund‐Richter L. , Reinholdsson G. , Roberts T. M. , Schaffhausen B. S. , Dalianis T. 
Published: February 2007

AbstractThe relationship between the polyoma virus tumor‐specific transplantation antigen (TSTA) and 2 of the virus proteins coded from the early region of polyomavirus was investigated. Mice were immunized with small T antigen and a truncated mutant of middle T antigen, both purified from genetically engineered Escherichia coli. The 2 proteins induced protective immunity against polyomavirus‐induced tumors, but not against non‐polyoma tumors, indicating that one or more of the polyoma T antigens are directly involved in a TSTA function.
Recombinant human leukocyte interferon‐α 2b stimulates the synthesis and release of a 90k tumor‐associated antigen in human breast cancer cells
Authors: Iacobelli S. , Scambia G. , Natoli C. , Panici P. Benedetti , Baiocchi G. , Perrone L. , Mancuso S. 
Published: February 2007

AbstractWe have previously reported the production of a new monoclonal antibody (MAb) (SP‐2) recognizing a 90‐kDa tumorassociated antigen, termed 9OK, which is increased in the serum of many cancer patients. Treatment of CG5 human breast cancer cells with recombinant interferon‐α 2b (rlFN‐α 2b) can increase the synthesis and release, in culture medium, of the 90K. The effect of rIFN‐α 2b was dose‐related and occurred at concentrations which did not affect cell proliferation. The increase of 90K expression was due to de novo protein synthesis since cycloheximide, added within 3 hr of the beginning of rIFN‐α 2b stimulation treatment, completely abolished the effect of rlFN‐α 2b. The stimulatory effect of rIFN‐α 2b was already evident after 24 hr treatment. Finally, an increase in serum 90K levels was observed in 3 patients with advanced breast cancer receiving a short course of rIFN‐α 2b (Intron A). No effect of rIFN‐α 2b was seen in 3 normal women. The ability of rIFN‐α 2b to increase the synthesis and release of 9OK both in vitro and in vivo may be of clinical importance in the early detection of tumors.
Transformation of primary human fibroblast cells with human papillomavirus type 16 DNA and Ej‐ras
Authors: Matlashewski Greg , Osborn Kit , Banks Lawrence , Stanley Margaret , Crawford Lionel 
Published: February 2007

AbstractHuman papillomavirus type 16 (HPV type 16) has been implicated as an etiological agent in human cervical cancer. This virus contains sequences which, under the proper transcriptional control, can increase the tumorigenicity of established mouse cells and cooperate with EJ‐ras in transforming primary baby rat kidney (BRK) cells. These data argue that this virus contains oncogenic sequences. Because this is a human virus, it was important to study the effect on primary human cells of HPV type‐16 DNA in both the presence and absence of EJ‐ras. We now present data which demonstrate that HPV type‐16 DNA, under the transcriptional control of Moloney murine leukemia viral long terminal repeats (MoMulV‐LTR), can extend the life span of primary human fibroblast cells in culture. Co‐transfection of the HPV type‐16 DNA containing plasmid together with an activated EJ‐ras oncogene gives rise to transformed cells which grow faster, are morphologically different from and more aneuploid than cells established with only HPV type‐16 DNA. Molecular analysis of these established and partially transformed human cells reveals that they contain and express the transfected DNA. These data argue that primary human cells can be transformed with HPV type‐16 and EJ‐ras sequences, whereas cells harboring only HPV type 16 DNA are largely normal but have an extended life span.
Inflammation and anti‐tumor resistance. IV. Induction of cytostatic activity of murine peritoneal cells by a mouse granuloma protein
Authors: Fontan Elisabeth , Fauve Robert M. 
Published: February 2007

AbstractPeritoneal cells from C57B1/6 mice, incubated in vitro with a pure mouse granuloma protein (MGP), decreased growth of Lewis tumor cells (3LL). This cytostatic activity was due to the release of stable cytostatic factors as determined by reduction of 125iododeoxyuridine (125I‐UdR) incorporation in target cell cultures. Resident, inflammatory or bone‐marrowderived macrophages incubated with MGP had no cytostatic effect on tumor cells. Co‐operation between lymphocytes and macrophages was required to express cytostasis when these cells were exposed to MGP. Maximal production of this factor by peritonear cells was detected in the medium after treatment with MGP for 6 hr. Cytostatic activity was thermolabile (I hr/56°C). Fractionation of peritoneal cell supernatant by HPLC resulted in the recovery of one peak, eluting at 70 kDa, which was cytostatic for 3LL cells. The cytostatic supernatant was tested for tumor necrosis factor activity (TNF): no correlation between TNF and cytostatic activity was observed. Indeed, even high amounts of mouse rTNF did not affect 3LL cell growth. Moreover, monoclonal antibodies (MAbs) to mouse TNF had no effect on cytostasis, indicating absence of synergistic interactions of the cytostatic factor with low levels of mouse TNF.
Weight, height and body mass index in the prognosis of breast cancer: Early results of a prospective study
Authors: Hebert James R. , Augustine Annamma , Barone Jeanine , Kabat Geoffrey C. , Kinne David W. , Wynder Ernst L. 
Published: February 2007

AbstractThe hypothesis that obesity plays a role in the prognosis of breast cancer is examined in this preliminary analysis of a follow‐up study of 472 early‐stage breast cancer patients. The 75th percentile values of weight (= 73 kg) and body mass index (BMI = 28) in the total patient population were taken as the cut points for estimating overweight or “obesity”. Stratified, survival, and logistic regression analyses showed that increased weight or BMI, but not height, were associated with increased risk recurrence. In the logistic regression analysis, after accounting for other risk factors, stage III was a negative prognostic indicator of recurrence (with stage I as the referrent group, OR = 3. 46, 95% Cl: 1.36–8.81). Women whose weights were above the 75th percentile value had a significantly increased risk of recurrence in relation to the other women (OR = 3.55%, 95% Cl: 1.65–7.65). Results from a model substituting BMI for weight showed a similar significant result. The adequacy of using anthropometric indices as proxies for obesity and various biological mechanisms, which may explain the relationship, are discussed.
Cigarette smoking, alcohol consumption and primary liver cancer: A case‐control study in the USA
Authors: Yu He , Harris Randall E. , Kabat Geoffrey C. , Wynder Ernst L. 
Published: February 2007

AbstractCigarette smoking and alcohol consumption were examined as potential risk factors in a case‐control study of primary liver cancer (PLC). A total of 165 PLC cases and 465 matched controls from several US hospitals were studied. A weak but statistically significant (p <0.05) dose‐response relationship was observed between alcohol consumption and PLC in elderly females independent of other major risk factors (adjusted OR = 1.87 and 3.48 for 1–2 and >3 drinks per day, respectively) and a similar trend was evident in elderly males. The risk for PLC was also elevated in elderly females who were current cigarette smokers (adjusted OR = 3.30). Our results suggest that alcohol consumption and cigarette smoking may have minor age‐ and sex‐specific effects on the development of PLC, and underscore the need for further investigations to elucidate major PLC risk factors in US populations.
Intraoperative radioimmunolocalization of colorectal carcinoma with a hand‐held gamma probe and MAb B72.3: Comparison of in vivo gamma probe counts with in vitro MAb radiolocalization
Authors: Tuttle Steven E. , Jewell Scott D. , Mojzisir Cathy M. , Hinkle George H. , Colcher David , Schlom Jeffrey , Martin Edward W. 
Published: February 2007

AbstractA new intraoperative approach to tumor localization using radiolabelled monoclonal antibody (MAb) B72.3 involves the use of a hand‐held gamma‐detecting probe (GDP) by the surgeon and, subsequently, the pathologist. We report here the use of 125j‐labelled MAb B72.3 IgG and a GDP to localize primary and metastatic colorectal cancer in 31 patients. The patients were administered radiolabelled MAb i. v., and all underwent surgical exploration 5 to 35 days post‐injection. In vivo localization of the MAb was evaluated using a GDP, with tumor and normal tissue counts being obtained. In each case, the subsequent tumor and normal tissue that were resected were analyzed in vitro for MAb localization; this was evaluated by calculating the radiolocalization index, i. e., the ratio of the injected dose per gram localized to tumor versus that of normal tissue. When the GDP was used intraoperatively, MAb B72.3 localized tumors in 68% (21/31) of the patients; the arbitrary criterion of tumor‐to‐normal tissue ratios higher than or equal to 2.0: I in vivo being taken as positive. Resected tumor radiolocalization indices ranged from 0.5 to 543, and 71% (22/31) of the patients studied had tumors with radiolocalization indices higher than or equal to 3. Of 50 carcinoma biopsies, 34 that were probe‐positive were antigen‐positive when B72.3 was used in immunoperoxidase assays, while 4 carcinoma biopsies that were probe‐negative were also antigen‐negative. Twelve of 50 biopsies were probe‐negative and antigen‐positive, but many of these lesions only contained a few antigen‐positive cells; none of the 50 was probe‐positive and antigen‐negative. Tumors of all histologic grades localized injected MAb and, in general, higher in vivo probe ratios and radiolocalization indices were obtained from patients who underwent surgery 20 to 35 days following injection of the MAb. MAb B72.3 localized tumor in all sites to which colon carcinoma commonly metastasizes, including mesenteric and peri‐aortic lymph nodes, liver, lung, and peri‐rectal soft tissue. There was a strong statistical correlation (p = 0.001) between detecting MAb B72.3 localization to tumors using the GDP intraoperatively and subsequent in vitro analysis of cpm/g for tumor versus normal tissues. These studies thus further validate the use of 125I‐labelled MAb B72.3 IgG and of a hand‐held gamma probe for the intraoperative detection of carcinomatous lesions.
Enhancement of the antiproliferative effect of cis‐diamminedichloroplatinum(II) and nitrogen mustard by inhibitors of protein kinase C
Authors: Hofmann Johann , Doppler Wolfgang , Jakob Axel , Maly Karl , Posch Lydia , Überall Florian , Grunicke Hans H. 
Published: February 2007

AbstractQuercetin (3, 3′, 4′, 5, 7‐pentahydroxyflavone) has been shown to inhibit a variety of enzymes including the calcium‐ and phospholipid‐dependent protein kinase (protein kinase C) in vivo and in vitro. We show that this compound synergistically enhances the antiproliferative activity of cis‐diamminedichlo‐roplatinum(II) (cis‐DDP) and nitrogen mustard. Quercetin does not affect the repair of DNA interstrand cross‐links introduced by cis‐DDP. Long‐term exposure to 12‐O‐tetradeca‐noylphorbol‐13‐acetate (TPA), which reduces total protein kinase C activity, also amplifies the growth‐inhibitory effect of cis‐DDP and acts synergistically with quercetin. A synergism is also observed if tamoxifen or staurosporine are combined with cis‐DDP. For both drugs the dose‐effect curves for the inhibition of protein kinase C closely resemble the dose‐effect curves for the antiproliferative activities. Although alternative mechanisms cannot be definitively excluded, the effects of quercetin, TPA, tamoxifen and staurosporine may result from the inhibition of protein kinase C.
Heterogeneity of human lymphokine (IL‐2)‐activated killer (LAK) precursors and regulation of their LAK induction by blood monocytes
Authors: Sone Saburo , Inamura Noriaki , Nii Akihiko , Ogura Takeshi 
Published: February 2007

AbstractHighly purified lymphocytes (> 99%) and monocytes (>90%) were isolated by CCE from peripheral blood of healthy donors. Blood lymphocytes were separated by this CCE into 9 subpopulations. The NK activities of these lymphocyte fractions against NK‐sensitive K‐562 cells and their LAK activities against NK cell‐resistant target (Daudi) cells were assayed promptly or after incubation of the fractions for 4 days with or without an optimal concentration of IL‐2. NK and LAK activities were measured by 4‐hr 51Cr‐release assay. On the basis of their NK and LAK activities, these lymphocyte fractions were classified into 3 subpopulations of LAK precursors: one lacking both NK and LAK activities (Fr. 2), one with moderate NK activity but low LAK activity (Fr. 5), and one possessing both NK and LAK activities (Fr. 8). Addition of autologous fresh monocytes to the lymphocyte cultures resulted in a significant increase in induction of LAK activity in Fr. 2 and Fr. 5. This up‐regulation of lymphocytes in Fr. 2 and Fr. 5 by monocytes was confirmed in parallel experiments by measuring the blastogenic response of the lymphocytes to IL‐2. Depletion of lymphocytes in Fr. 8 of CD16+ (Leu‐11+) NK cells resulted in 74% reduction in LAK induction, whereas depletion of mixtures of monocytes and lymphocytes in Fr. 2 of cells reacting with CD3+ (OKT3+) antibody resulted in a 66% reduction in LAK induction. This up‐regulation of LAK cell induction from LAK precursors by monocytes was confirmed using 4 lines of human lung cancer cells as targets for LAK activity. These results clearly indicate that human monocytes may cause up‐regulation of the expression of IL‐2‐in‐duced LAK activity in T cells and in a subpopulation of NK cells.
C‐myc expression and transformed phenotypes in hybrid clones between mouse plasmacytoma S194 cells and normal spleen cells or fibroblasts
Authors: Oikawa Tsuneyuki , Yuhki Yuhko , Kondoh Nobuo , Abe Kenji , Yuhki Naoya , Ogiso Yoshifumi , Kuzumaki Noboru 
Published: February 2007

AbstractExpression of the rearranged c‐myc oncogene and transformed phenotypes was investigated in 2 different types of somatic cell hybrid clones between a BALB/c mouse plasmacytoma line (S194) and normal allogeneic spleen cells or fibroblasts. In the parental S194 cells, one allele of the c‐myc was rearranged and its 5′ flanking region was partially deleted by recombination with the immunoglobulin C α gene. Due to this recombination, S194 cells expressed approximately 20‐fold higher than normal spleen or fibroblast levels of c‐myc transcripts from the rearranged allele, which are smaller than normal germ‐line 2.4‐kb c‐myc transcripts, but they expressed the same low levels of 2.4‐kb c‐myc transcripts from the nonrearranged allele as compared with normal spleen cells or fibroblasts. All the hybrid clones retained both the rearranged and the non‐rearranged c‐myc. The hybrid clones between S194 and normal spleen cells showed transformed phenotypes and expressed the same high levels of rearranged c‐myc transcripts and low levels of the non‐rearranged c‐myc transcripts as the parental S194 cells. On the other hand, the hybrid clones between S194 cells and normal fibroblasts showing nontransformed phenotypes inhibited expression of the rearranged c‐myc to undetectable levels but expressed the nonrearranged c‐myc transcripts at low levels. A hybrid clone between S194 cells and normal fibroblasts showing transformed phenotypes also exhibited the same pattern of c‐myc expression as the non‐transformed hybrid clones. These results indicate that expression of the rearranged c‐myc in S194 mouse plasmacytoma cells is modulated in different ways in different components of cell lineages, although the correlation between the levels of rearranged c‐myc transcripts and the transformed phenotypes in the hybrid clones was not absolute.