bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic distribution of HTLV‐I and identification of a new high‐risk population
Authors: Levine Paul H. , Blattner William A. , Clark Jeffrey , Tarone Robert , Maloney Elizabeth M. , Murphy Edward M. , Gallo Robert C. , Robert‐Guroff Marjorie , Saxinger W. Carl
Published: February 2007

Epidemiologic studies indicate that human T‐cell lymphotropic virus type I (HTLV‐I), the causative agent of most cases of adult T‐cell leukemia/lymphoma (ATLL) in Southeast Japan and the Caribbean islands and the probable cause of a progressive neurological disorder often referred to as tropical spastic paraparesis, occurs with unusual geographic clustering. The current large‐scale serosurvey was undertaken to improve our understanding of HTLV‐I prevalence in different parts of the world. We analyzed 43,445 serum samples collected from various geographic locaies worldwide; 76% of these sera came from clinically healthy donors. Samples were initially screened by an enzyme‐linked immunosorbent assay (ELISA) and 4,353 were further evaluated by means of competition assays. In this study, which did not include sera from endemic areas of Japan, a high prevalence of infection was observed in several countries in the Caribbean basin. A significant age‐sex difference was observed between populations in the Caribbean and non‐endemic regions of Japan. The reason for the male excess in non‐endemic areas of Japan will require further study, while the female excess in the Caribbean basin is compatible with the previously described pattern for other HTLV‐I‐endemic areas. A newly recognized area of possible endemicity was southern Florida, where evidence of infection with HTLV‐I or a related virus was found in a group of native Americans whose sera were collected in 1968. In certain parts of the world, particularly sub‐Saharan Africa, important problems in determining specificity of reactivity occurred, probably because of cross‐reacting antibodies. No pattern was detected that could explain the cross‐reactivity solely on the basis of geographic areas, specific patterns of non‐viral parasitic infection, or methods of handling the specimens. It is possible that these cross‐reactivities are antibodies to proteins from HTLV‐I‐reiated retroviruses yet to be discovered.
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

It 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

Splenocytes 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

Serotherapy 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

Three 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

We 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

The 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

We 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

Human 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

Peritoneal 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

The 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

Cigarette 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

A 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

Quercetin (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

Highly 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

Expression 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.
Sensitivity of human glioma cells to cytotoxic heteroconjugates
Authors: Colombatti Marco , Bisconti Massimo , Dell'Arciprete Lorena , Gerosa Massimo A. , Tridente Giuseppe
Published: February 2007

Several anti‐human glioma cytotoxic conjugates were studied in vitro. Monoclonal antibodies (MAbs) to the GE 2 gliomaassociated antigen (anti‐GE 2) and MAbs to HLA‐DR antigens (D1/12) or human diferric transferrin (Tfn) were linked to the potent cytotoxin ricin (anti‐GE 2‐ricin) or to its A subunit (anti‐GE 2‐RTA, D1/12‐RTA, Tfn‐RTA). Anti‐GE 2‐RTA had low cytotoxic activity in both the absence and the presence of lysosomotropic substances inhibiting intracellular degradation. Anti‐GE 2‐rich was about 1,000 times more toxic than RTA alone, but showed only 14‐fold target specificity. D1/12‐RTA was about 20 times more toxic than RTA and its cytotoxic effect increased about 6‐ to 7‐fold when cell‐surface HLADR antigen expression was enhanced by IFN‐γ treatment. Human diferric Tfn linked to RTA demonstrated the highest cytotoxic activity, being about 5,000 times more toxic than RTA alone for glioma cells and about 6,000 times more toxic for Jurkat cells in the presence of the carboxylic ionofore monensin. Rich toxin was only about 5 times more toxic for Jurkat and glioma cells than Tfn‐RTA‐monensin. Tfn‐RTA was over 100,000 times more potent than the chemotherapeutic agent BCNU in reducing glioma cell survival in vitro. Addition of 80% human pooled cerebrospinal fluid (CSF) reduced Tfn‐RTA toxicity about 10‐fold. Kinetics of Tfn‐RTA cytotoxicity at non‐saturating concentrations indicated that over 80% of target cells could be killed within 8–10 hr in the absence and within 10–12 hr in the presence of human pooled CSF.
Liposoluble vitamins and lipid parameters in breast cancer. A joint study in northern Italy and southern France
Authors: Gerber Mariette , Cavallo Franco , Marubini Ettore , Richardson Sylvia , Barbieri Angelo , Capitelli Enrica , Costa Alberto , De Paulet André Crastes , De Paulet Pierrette Crastes , Decarli Adriano , Pastorino Ugo , Pujol Henri
Published: February 2007

The relationship between breast cancer, liposoluble vitamins, cholesterol and triglycerides was investigated by means of a hospital‐based case‐control study conducted at Milan (Italy) and Montpellier (France). These parameters were measured in blood samples taken from 319 cases and 344 controls. The interview included an evaluation of dietary intake of liposoluble vitamins. No difference emerged in liposoluble vitamin consumption, whereas a statistically significantly higher serum level of cholesterol and plasma level of vitamin E existed in cases compared to controls. The difference in plasma vitamin E was confirmed after adjustment for total cholesterol and triglycerides. In contrast, vitamin A variations appear to follow triglyceride trends. A multivariate analysis of the vitamin E plasma level was performed after classification of cases and controls according to quintile distribution of controls. All known risk factors plus age, serum total cholesterol and triglycerides were used as covariates. The odds ratio value for the highest quintile of plasma vitamin E is: 4.2 (1.9–9.0).
Familial and sporadic breast cancer cases in Iceland: A comparison related to ABO blood groups and risk of bilateral breast cancer
Authors: Tryggvadottir Laufey , Tulinius Hrafn , Robertson James McD.
Published: February 2007

This study was aimed at determining whether the familial clustering often observed in breast cancer is associated with genetic factors. We compared familial and sporadic breast cancer cases with respect to ABO blood group distribution and the risk of bilateral disease, using the data from the lcelandic Cancer Registry which contains genealogical information for about 30% of the breast cancer cases diagnosed in lceland since 1911. Cases were classified as familial if at least one first‐degree relative had breast cancer. Using this criterion, we identified 184 familial cases and 572 sporadic cases. The familial cases had a 2‐fold higher prevalence of blood group B than did the sporadic cases, and the frequency of this blood group in non‐affected relatives of cases was significantly reduced. Familial cases were about 2.7 times more likely to suffer from bilateral breast cancer than were the sporadic patients. These results support the presence of a genetic factor in the etiology of familial breast cancer.
Amplification of the EGF receptor and c‐myc genes in human esophageal cancers
Authors: Lu Shih‐Hsin , Hsieh Ling‐Ling , Luo Feng‐Chi , Weinstein I. B.
Published: February 2007

The incidence of esophageal cancer is extremely high in Linxian County and certain other regions of the People's Republic of China. Epidemiologic and laboratory studies suggest that N‐nitroso carcinogens and other environmental factors play a causative role. In the present study, employing over 100 DNA samples obtained from Lin‐xian patients who underwent surgery for esophageal cancer, we have found a significant frequency of amplification of either the human epidermal growth factor receptor (HER‐I) gene or the c‐myc oncogene. These changes were found not only in tumor specimens, but also in adjacent non‐tumor (grossly normal) tissue specimens obtained from patients with esophageal cancer. RNA samples were also obtained from over 30 tissue samples. These revealed considerable variation in the abundance of HER‐I and c‐myc transcripts in both the tumor and adjacent non‐tumor specimens. A few samples revealed extremely high levels of these transcripts. Thus, changes in gene copy number or level of expression of HER‐I or c‐myc DNA sequences may play an important role in the pathogenesis of esophageal cancer in this high‐risk region.
The international incidence of childhood cancer
Authors: Parkin D. M. , Stiller C. A. , Draper G. J. , Bieber C. A.
Published: February 2007

The International Agency for Research on Cancer has coordinated a worldwide study of the incidence of cancer in childhood. Contributors from over 50 countries have provided data. This paper presents a summary of some of the major results. The incidence rates and relative frequencies of childhood cancers are described according to I2 diagnostic groups, defined mainly in terms of tumour morphology. Variations in the risk of those tumours between different countries and different ethnic groups provide important information on the relative importance of environmental and genetic factors in their aetiology.
DNA content and genetic evolution of human colorectal adenocarcinoma. A study by flow cytometry and cytogenetic analysis
Authors: Remvikos Y. , Mulens M. , Vielh Ph. , Salmon R. J. , Dutrillaux B.
Published: February 2007

We have conducted in parallel DNA flow cytometry (FCM) and cytogenetic (CG) analysis of a series of surgical specimens from 35 human colorectal adenocarcinomas. An excellent quantitative correlation was observed (r = 0.99) between modal peak values of FCM histograms and chromosome counts. This observation confirms that aneuploidy, as defined by FCM, accurately reflects the deviation from diploidy of the genomic DNA. FCM‐derived DNA patterns have been analyzed in the context of the clonal chromosomal evolution determined by CG analysis. In the metaphases of a given tumor, even if karyotypes of different ploidy exist, the presence of identical marker chromosomes suggests a common origin for the multiple populations observed by FCM. Thus, heterogeneity in DNA content within a tumor, including the polyploidization step, would be indicative of genetic evolution.
Human breast and colon carcinomas express cysteine proteinase activities with pro‐aggregating and pro‐coagulant properties
Authors: Grignani Guido , Falanga Anna , Pacchiarini Lucia , Alessio Maria Grazia , Zucchella Marisa , Fratino Pietro , Donati Maria Benedetta
Published: February 2007

We have investigated concomitantly the pro‐aggregating and pro‐coagulant activities of II breast and 2 colon human carcinomas. Tumor tissues, obtained at surgery, were immediately processed to prepare tumor‐cell suspensions for the study of aggregating activity and tissue extracts for the study of procoagulant capacity. Nine carcinomas (8 breast and I colon) possessed a high, dose‐dependent platelet‐aggregating activity, which was present in the cell‐free supernatant and was inhibited by HgCI2 and iodoacetic acid, specific cysteine proteinase inhibitors, while apyrase and hirudin had no significant effect; in contrast, the other tumors did not aggregate platelets. All the tumor extracts tested from 12 carcinomas (II breast and I colon) were able to activate blood coagulation in both the presence and the absence of F VII. The activity was inhibited by HgCI2 and iodoacetamide, while Con A was less effective. Therefore, these tumors do not aggregate platelets through the production of ADP or thrombin, nor promote blood coagulation through the production and release of tissue factor; a tumor‐associated cysteine proteinase plays a major role in both pro‐aggregating and pro‐coagulant activities.
Formation of DNA adducts in human skin maintained in short‐term organ culture and treated with coal‐tar, creosote or bitumen
Authors: Schoket Bernadette , Hewer Alan , Grover Philip L. , Phillips David H.
Published: February 2007

Adult and foetal human skin samples maintained in shortterm organ culture were treated topically with solutions of coal‐tar, creosote or bitumen, then DNA was isolated and analysed by 32P‐post‐labelling for the presence of aromatic DNA adducts. Autoradiographs of the 32P‐labelled adducts resolved on polyethyleneimine‐cellulose tlc sheets revealed a band of radioactivity indicative of the formation of adducts by a large number of components in these complex carcinogenic mixtures. Single doses of the materials, similar to those used to initiate tumours in experimental animals, resulted in the formation of approximately 0.3 fmol total adducts/μg DNA. The levels of adducts formed in human skin are thus similar to those formed in mouse skin after administration of doses known to be carcinogenic to the latter. The results provide direct evidence of DNA damage in human skin by materials strongly suspected of being carcinogenic to humans, and point to a method for evaluating other complex mixtures of aromatic chemicals for their potential carcinogenic hazard.
Rapid selection of cultured cells with increased expression of a membrane marker (secretory component)
Authors: Kvale Dag , Bartek Jiri , Sollid Ludvig M. , Brandtzaeg Per
Published: February 2007

This study showed how immunomagnetic monodisperse microspheres (Dynabeads) can be used for rapid selection of stable and homogeneous sublines of cancer cells. The beads were activated with antibody to a specific surface membrane marker. We used a monoclonal antibody (MAb) to human secretory component (SC), the epithelial receptor for polymeric immunoglobulins (plg). A relatively low number of particles favored rosetting of strongly positive cells. SC‐expressing cells were isolated within 30 min from a colonic carcinoma cell line (HT‐29.E10). After 13 months of continuous culture the selected cells had a 15 times higher cellular content and a 10 times higher secretory rate of SC than parallel cultures of the original cell line. Immunomagnetic microspheres can be recommended in experimental cancer research, e. g., in order to minimize cellular heterogeneity and to isolate cells with particular surface membrane phenotypes in differentiation studies. The selection method is rapid and simple, and eliminates laborious test systems for conventional subclone screening.
Epidemiology of HTLV‐i in gabon (western equatorial Africa)
Authors: Delaporte Eric , Dupont Alain , Peeters Martine , Josse Richard , Merlin Marcel , Schrijvers Dirk , Hamono Bernard , Bedjabaga Léonard , Cheringou Henri , Boyer Franck , Brun‐Vézinet Françoise , Larouzé Bernard
Published: February 2007

In 1986 a survey to determine the distribution of HTLV‐I infection was conducted in Gabon in a representative sample of adults and children. Five samples were taken in adults and 2 samples in children living in urban and rural areas. Samples were taken by the cluster sampling technique, i. e., clusters of randomly selected households. Sera were tested for IgG antibodies to HTLV‐I by ELISA. ELISA‐positive sera were retested by Western blot. The study comprised 1,874 adults and 6B4 children, all apparently healthy. In the adults the crude prevalence rates of anti‐HTLV‐I antibodies ranged from 5.0% in urban areas to 10.5% in the southern province. In rural areas, the age‐adjusted prevalence rate (9.1%) was significantly higher than in urban areas (5.0%) (p<0.01), In children there was no significant difference between urban (2.4%) and rural (2.0%) prevalence rates. Prevalence increased with age but was not related to sex. This survey shows that HTLV‐I infection is common in Gabon but varies considerably by region.
DNA flow cytometric analysis indicates that many breast cancers detected in the first round of mammographic screening have a low malignant potential
Authors: Kallioniemi Olli‐Pekka , Kärkkäinen Alpo , Auvinen Ossi , Mattila Jorma , Koivula Timo , Hakama Matti
Published: February 2007

An organized mammographic screening program covered 8,690 women from selected birth cohorts (aged 50–59) in the Tampere University Central Hospital district. Forty‐four breast cancer cases were detected in the first round of mammographic screening, which is 3.7 times the expected annual number of new cases in this population. To evaluate the proliferative kinetics and biological properties of these cancers, DNA flow cytometric analysis was carried out in 37 of the screen detected cancers (SDCs) using 60 clinically detected stage 1–11 cancers and 30 screen‐detected benign lesions as reference. DNA aneuploidy was observed in 17/37 (46%) of the SDCs as compared to 41/60 (68%) in the clinical controls (p < 0.05), while all the benign lesions were DNA‐diploid. The median S‐phase fraction (SPF) in the SDCs was significantly (P < 0.001) lower (3.5%) than in the clinical controls (9.6%). Differences in SPF persisted in subgroups defined by DNA ploidy and histological type. In stage‐I SDCs the median SPF value (2.5%) approached that of benign tumors (1.9%). Our epidemiological and biological data indicate that the first round of mammography predominantly detects prevalent preclinical lesions, some of which are of very low malignant potential. At present such patients may often receive too extensive treatment. DNA flow cytometry could help in the identification of cases which could be treated, for example, by breast‐conserving methods.
Relationship between DNA ploidy, antigen expression and survival in renal cell carcinoma
Authors: Oosterwijk E. , Warnaar S. O. , Zwartendijk J. , Van Velde E. A. Der , Fleuren G. J. , Cornelisse C. J.
Published: February 2007

Tumor ploidy and expression of renal differentiation antigens as recognized by a previously described series of monoclonal antibodies (MAbs) (RC2, RC3, RC4, RC38, RC69, RC154 and G250) were assessed in 48 renal‐cell carcinomas. A positive association was found between aneuploidy and development of metastases. Aneuploid tumors showed a loss of antigen expression more frequently than diploid tumors. This difference was statistically significant for antigens recognized by RC3 and RC69. Loss of RC154 reactivity was associated with increased metastatic potential. Clinical stage was the most powerful single prognostic variable but ploidy and RC3 reactivity carried additional prognostic information.
Interleukin‐1 and tumor necrosis factor production by tumor‐associated mononuclear leukocytes and peripheral mononuclear leukocytes in cancer patients
Authors: Economou James S. , Colquhoun Steven D. , Anderson Timothy M. , McBride William W. , Golub Sidney , Holmes E. Carmack , Morton Donald L.
Published: February 2007

The production of interleukin‐I (IL‐I) and tumor necrosis factor (TNF) by tumor‐associated mononuclear leukocytes (TAML) and peripheral mononuclear leukocytes (PBML) from 9 otherwise untreated patients with a variety of malignancies (lung, sarcoma, stomach, renal) was assessed. Cells were cultured for 24 hr in vitro in the presence or absence of lipopolysaccharide (LPS), and IL‐I and TNF levels were measured in culture supernatants. TNF production was comparable between TAMLs and PBMLs. However, a striking defect in IL‐I production by TAMLs was noted. There was no basal production of IL‐I and LPS‐stimulated TAMLs produced only 1% the amount of IL‐I produced by LPS‐stimulated PBMLs.
Plasma membrane lipid composition of vinblastine sensitive and resistant human leukaemic lymphoblasts
Authors: May George L. , Wright Lesley C. , Dyne Marlen , MacKinnon Wanda B. , Fox Richard M. , Mountford Carolyn E.
Published: February 2007

Plasma membranes purified 32‐ to 45‐fold were isolated from leukaemic T‐lymphoblasts, both sensitive and resistant to the Vinca alkaloid vinblastine. On development of drug resistance there was a very significant elevation of ether lipid content. I‐0‐alkyl phospholipid increased by 200% with a smaller 30% increase in I‐0‐alkenyl phospholipid. Cholesterol and phospholipid levels were also found to increase by 50% and 30% respectively, while the lipid to protein ratio increased by 60%. More modest changes were observed in the fatty acid composition of the membranes, with an alteration in the double bond index from 35.3 to 41.2. These lipid changes may have important implications in the changes to membrane permeability that develop with drug resistance.
Cultured, aids‐related Kaposi's sarcoma cells express endothelial cell markers and are weakly malignant in vitro
Authors: Roth Willy Kurt , Werner Sabine , Risau Werner , Remberger Klaus , Hofschneider Peter Hans
Published: February 2007

Up to 30% of patients with acquired immunodeficiency syndrome (AIDS) suffer from Kaposi's sarcoma (AIDS‐KS). The histogenesis and neoplastic nature of this tumor is still controversial. We have established cell cultures of KS biopsies from 7 patients with AIDS. All donors were seropositive for the human immunodeficiency virus I (HIV‐I), cytomegalovirus (CMV) and hepatitis B virus (HBV). The tumors were histologically shown to be KS. Cell cultures derived from these tumors all expressed the endothelial cell marker BMA 120 antigen. Most of these cultures were positive for acetylated low‐density lipoprotein (acLDL) uptake and alkaline phosphatase (AP) expression, and negative for factor‐VIII‐related antigen (FVIII‐RAg). The staining pattern was heterogeneous with respect to number of endothelial cell markers expressed in each culture. We conclude from subcloning experiments that the cultured cells cease to express acLDL receptor and AP, but not the antigen detected by the monoclonal antibody (MAb) BMA 120. The cells grew well in culture up to 50 passages and showed a fibroblast‐like morphology. Assays performed to investigate their degree of malignancy revealed a significantly increased passage number under reduced serum conditions as compared to normal fibroblasts but no tumor formation in nude mice. Neither HIV, HBV nor CMV sequences were found in any of the cell lines tested. We conclude that AIDS‐KS is an endothelial‐cell‐derived neoplasm of low malignancy and that HIV, HBV and CMV are not directly involved in its genesis.
Evaluation of four CD22 antibodies as ricin a chain‐containing immunotoxins for the in vivo therapy of human B‐cell leukemias and lymphomas
Authors: Shen Guo‐Liang , Li Jia‐Ling , Ghetie Maria‐Ana , Ghetie Victor , May Richard D. , Till Mark , Brown Alex N. , Relf Michele , Knowles Phillip , Uhr Jonathan W. , Janossy George , Amlot Peter , Vitetta Ellen S. , Thorpe Philip E.
Published: February 2007

Ricin A chain‐containing immunotoxins (IT‐As) specific for the human B‐cell antigen, CD22, were prepared from 4 monoclonal antibodies (MAbs) or their Fab′ fragments: RFB4, HD6, UV22‐1 and UV22‐2. The ITs were tested for their ability to kill cells from the Burkitt lymphoma line, Daudi, the pre‐B‐cell leukemia line, NALM‐6, and the myeloma cell line, ARH‐77. Daudi expresses high levels of CD22, whereas NALM‐6 and ARH‐77 express low levels of CD22. The IgG‐RFB4‐A was highly toxic to all 3 cell lines; it killed 50% of the Daudi cells at a concentration of 1.2 × 10‐12 M and 50% of NALM‐6 and ARH‐77 cells at concentrations of 1.5 to 2.1 × 10 −11 M. IgG‐RFB4‐A was 10–30 times more toxic to Daudi cells than were the IgG‐As constructed from the other 3 CD22 MAbs and 10 times more toxic than ricin itself. IT‐As constructed from the Fab′ fragments of the 4 CD22 antibodies were 2 to 5 times less toxic to Daudi cells than their IgG‐A counterparts. Fab′‐RFB4‐A was twice as toxic to Daudi cells as ricin, whereas the other Fab′‐As were about 7 times less toxic than ricin. Scatchard analyses of the binding of the radio‐iodinated antibodies to Daudi cells showed that the intact RFB4 antibody bound 3–10 times more strongly than the other antibodies, whereas the Fab′‐RFB4 bound 1.2 to 3.5 times more strongly than the Fab′ fragments prepared from the other antibodies. Thus, the potent cytotoxic activity of the RFB4‐As appears to derive, in part, from their superior binding affinity. Prior studies have shown that UV22‐1 and HD6 cross‐react with certain normal human tissues lacking cells of B‐cell lineage, whereas UV22‐2 and RFB4 are B‐cell‐specific. This fact, together with its superior potency as an IT‐A, suggests that RFB4 is the antibody of choice for preparing Fab′‐As or IgG‐As for in vivo therapy of human B‐cell leukemias and lymphomas.
The value of screening as an approach to cervical cancer control in iceland, 1964‐1986
Authors: Sigurdsson Kristjan , Adalsteinsson Stefan , Tulinius Hrafn , Ragnarsson Jonas
Published: February 2007

The effect of screening for cervical cancer on time trends in incidence and mortality from that disease, and the occurrence of pre‐invasive cervical lesions during the period 1964–1986, were analyzed. After commencement of screening in 1964 all the above parameters increased for a short initial period but then fell markedly. From 1980, coinciding with a sharp rise in regular attendance rate, there was an increase in incidence up to 1984, followed by a decrease. The rate of pre‐invasive stages also increased from 1980, but appears to be levelling off. The cervical cancer mortality rate decreased significantly during the study period. In more recent years, a shift in the occurrence of cervical cancer and pre‐invasive lesions from older to younger women has been observed. Screening still appears to be effective in the control of squamous‐cell carcinomas of stages 1 B and over, but not of adeno‐ and adeno‐squamous carcinomas.