bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue‐specific markers in flow cytometry of urological cancers. III. Comparing chromosomal and flow cytometric dna analysis of bladder tumors
Authors: Smeets A. W. G. B. , Laarakkers L. , Pauwels R. P. E. , Beck J. L. M. , Vooijs G. P. , Ramaekers F. C. S. , Geraedts J. P. M. , Debruyne F. M. J. , Feitz W. F. J.
Published: February 2007

Thirty‐seven transitional‐cell carcinomas (TCC) of the urinary bladder were analyzed by DNA flow cytometry (FCM). After labelling of the cell suspensions with antibodies to cytokeratin, the cytokeratin‐positive cells and the non‐epithelial cytokeratin‐negative cells could be analyzed separately. After estimation of S‐ and G2M phase, 3/17 cases (18%) with a normal DNA index showed elevated proliferative levels, among cytokeratin‐labelled suspensions only. Of these 17 cases, 14 showed chromosomal abnormalities. The remaining 20 cases were abnormal, irrespective of the technique used. Although immuno‐labelling of tumor cells for cytokeratin in FCM increases the sensitivity of this method in detecting aneuploid tumors or tumors with high proliferation fractions, the discriminating power of chromosomal analysis of TCC is greater than FCM.
Mass screening for cervical cancer in øtfold county of norway 1959‐77
Authors: Magnus Knut , Langmark Frøydis , Andersen Aage
Published: February 2007

In 1959, the Norwegian Cancer Society started a research project in Østfold county to assess the effect of a mass screening program for cervical cancer. The program comprised 5 screening rounds during the period 1959‐77. At each screening a clinical gynecological examination was performed in addition to the cytological test. A total of 45,960 women aged 25‐59 years at the first screening were invited to participate. The follow‐up, which was based on the data base of the Cancer Registry of Norway, lasted until December 31, 1982. For the follow‐up period as a whole, the observed incidence and mortality were reduced to 78% and 83% of the expected values, respectively. Through the initial phase of the program there was a cumulation of patients with early‐stage disease, while the incidence of advanced disease and mortality were reduced. In the later part of the follow‐up period, a decrease in incidence of early and advanced disease as well as in mortality was observed. Women not participating in the screening program had a significantly higher risk of cervical carcinoma than the reference population, and a less favorable stage distribution as well. Among participants in the screening program, the reduction of risk was dependent upon the number of previous negative smears. Women with 5 previous negative smears had a risk of disease which was only 18% of that expected. Problems concerning choice of reference population, migration, attendance rates, sensitivity and specificity of the cytological tests and intervals between screenings are discussed. Also, the probable conversion rates of pre‐cancerous lesions to cancer and the health hazards involved in possible over‐treatment of pre‐cancerous cases which otherwise would have regressed, are considered. A dynamic model is suggested. In order to achieve a reduction of mortality in the short term, the efforts of the program should initially be concentrated on older women. To achieve a reduction of incidence in the long run, younger women should gradually be included. Finally, special efforts should be made to increase attendance rates among high‐risk women.
Characterization of 3ll‐tumor variants generated by in vitro macrophage‐mediated selection
Authors: Remels Linda M. , de Baetselier Patrick C.
Published: February 2007

Following sequential interactions between activated syngeneic Mϕs and 3LL tumor cells, stable Mϕ‐resistant 3LL variants were isolated. Unlike the unselected 3LL cells, these Mϕ‐selected variants were relatively resistant to the cytostatic and cytolytic activity of activated effector Mϕs. Such Mϕ‐resistant 3LL variants evade the Mϕ tumoricidal activity by at least two mechanisms. Firstly, they manifest a reduced susceptibility towards Mϕ‐related cytotoxins such as TNF. Secondly, they actively suppress the cytotoxic potential of Mϕs through secretion of Mϕ‐inhibitory factors. The resistance of the 3LL variants to Mϕ effector cells in vitro was reflected in vivo by a higher tumorigenic and metastatic potential. No strict correlation was found between the NK sensitivity of Mϕ‐resistant and Mϕ‐sensitive 3LL cells and their metastatic ability. Hence, activated tumoricidal Mϕs may play a central role in either the elimination or selection of neoplastic cells.
Epstein‐barr virus‐specific t‐cell recognition of B‐cell transformants expressing different ebna 2 antigens
Authors: Wallace L. E. , Young L. S. , Rowe M. , Rickinson A. B. , Rowe D.
Published: February 2007

Epstein‐Barr (EB) virus isolates can be classified as type A or type B depending upon the identity of the virus‐encoded nuclear antigen EBNA 2; the EBNA 2A and 2B proteins show limited amino‐acid homology and induce largely non‐cross‐reactive antibody responses in humans. To examine whether EBNA 2 might also be a target for virus‐specific cytotoxic T‐cell responses (like “intracellular” antigens in other viral systems), normal B cells from non‐immune donors of known HLA type were transformed in vitro with virus isolates either of type A (from the B95‐8 and IARC‐BL74 cell lines) or of type B (from the AG876 and IARC‐BL16 cell lines) to provide a suitable panel of target cells. DNA hybridization with type‐specific probes and immunoblotting with type‐specific antisera confirmed the EBNA 2 type of the resident virus in the various in vitro transformants. These cells were then tested as targets for virus‐specific cytotoxic T cells, the latter being prepared from type‐A virus‐infected donors by in vitro reactivation of memory cells from peripheral blood using autologous type‐A virus‐transformed cells as stimulators. Such effector cells lysed type‐A virus‐transformed and type‐B virus‐transformed target cells equally well, indicating that EBNA 2 (in particular that part of the protein which varies between virus types) seems not to be a dominant antigen for the induction of EB virus‐specific cytotoxic responses.
Production of stable cytolytic T‐cell clones directed against autologous human melanoma
Authors: Hérin M. , Lemoine C. , Weynants P. , Vessière F. , Van Pel A. , Boon T. , Knuth A. , Devos R.
Published: February 2007

We have attempted to optimize the production of stable human cytolytic T lymphocyte clones directed against autologous melanoma cell lines. MLTC were restimulated every week with irradiated melanoma cells in medium containing human serum and IL‐2. After 21 to 35 days, in 5 out of 6 patients, these cultures expressed a preferential cytolytic activity against the autologous melanoma cells, as compared to autologous EBV‐B cells or NK target K562. Limiting dilution of MLTC responder cells was performed at times varying from days 7 to 28, in medium containing IL‐2 and allogeneic EBV‐B cells as feeders. Approximately 1% of these responder cells gave rise to CTL clones that lysed the autologous melanoma cells, but did not lyse K562 or autologous B cells. It was possible to maintain in culture for several months a large number of CTL clones that retained this specificity with high activity, and multiplied more than 5‐fold every week. Some of these CTL clones were dependent on the presence of the autologous melanoma cells for their growth. With one melanoma, the use of autologous CTL clones made it possible to identify 3 different antigens on the tumor cells.
Role of MHC class‐i antigens and the CD3 complex in the lysis of autologous human tumours by T‐cell clones
Authors: Roberts T. E. , Shipton U. , Moore M.
Published: February 2007

Peripheral blood lymphocytes (PBL) of 4 patients with malignant effusions were stimulated for 6 days with purified autologous tumour cells, before isolation of the lymphoblasts and cloning by limiting dilution in interleukin‐2 (IL‐2). Fortyfive clones were analyzed for cytotoxicity (CTX) against autologous, allogeneic tumour and erythromyeloid K562 cells of known status with respect to expression of major histocompatibility complex (MHC) antigens, estimated by reaction with the W6/32 (anti HLA, ‐A, ‐B, ‐C monomorphic) and TDR 31.1 (anti HLA‐DR) monoclonal antibodies (MAb). All 45 clones were CD3+. Twenty‐five (56%) of them were cytotoxic for at least one target; 24 were autoreactive (restricted in 7); 17 were alloreactive; 16 were K562 reactive. Under comparable conditions autoreactivity was partially blocked by W6/32 in 12/20 effectoratarget combinations; alloreactivity in 8/13 and K562 reactivity in 0/14. Modulation of effector cell surface CD3 antigens by OKT3 monitored by flow cytometry reduced autoreactivity in 9/14 combinations, alloreactivity in 2/6 and K562 reactivity in 0/4. W6/32 blocking and T3 modulation of cytotoxicity were almost invariably concordant against the same target. The data suggest that, to accomplish lysis of autologous and allogeneic tumour targets, certain clones require MHC recognition and a functional CD3 complex, while for others with similar target cell repertoires, there is no such requirement. It is possible that T‐cell clones responding to a tumour‐associated antigen (TAA) in the context of self MHC antigens can also respond to an allogeneic class‐I product in the absence of TAA, and/or that aberrant class‐I antigen expression on autologous tumours accounts for the alloreactivity.
Evaluation of monoclonal antibodies for the detection of exfoliative nasopharyngeal carcinoma cells
Authors: Chan K. H. , Yip T. C. , Choy Damon , Chan C. W. , Zeng Y. , Ng M. H.
Published: February 2007

Exfoliative cells were aspirated from 15 patients suspected of having nasopharyngeal carcinoma (NPC) and showing the presence of lesions or other abnormalities in the nasopharynx. They were tested for binding with a 125I monoclonal antibody (MAb) (MA6) which is selectively reactive against human B lymphocytes and a variety of carcinomas. A positive result was obtained from 6/9 patients with, and from 0/5 patients without, histologically confirmed disease. One patient with eskimoma also gave a negative binding result. Cytology was specific but less sensitive, tumour cells being detected in 3 of the patients with confirmed disease. Immunocytology using MA6 was limited, like cytology, by poor recovery of the tumour cells and the results were in complete concordance with cytology. The other MAbs used were raised against carcinoembryonic antigen (CEA) and a carcinoma cell line (Ca2), respectively. The latter was not reactive against the NPC tumour cells while the CEA antibody was not sufficiently selective to be useful.
Dissociation between thromboxane generation and metastatic potential in cells from a murine fibrosarcoma. Studies with a selective thromboxane synthase inhibitor
Authors: Vicenzi Elisa , Lampugnani Maria Grazia , Dalessandro Anna Paola Bolognese , Niewiarowska Anna , De Gaetano Giovanni , Donati Maria Benedetta
Published: February 2007

Since the highly metastatic variant M4 of the mFS6 fibrosarcoma has the peculiar feature of generating larger amounts of immunoreactive thromboxane B2 (TxB2) than the nonmetastatic variant (M9), we used the thromboxane synthase inhibitor dazmegrel (UK‐38,485) in an effort to influence its metastatic potential. TxB2 formation by tumor cells freshly harvested from the primary tumor could be completely inhibited by drug addition in vitro. TxB2 generation was inhibited with a dose‐response curve, 2 μm being the lowest dazmegrel concentration giving 100% inhibition. Chronic treatment of tumor‐bearing mice with dazmegrel (150 mg/kg b.w. twice daily by gavage) from the day of tumor‐cell implantation until killing of the animals caused a more than 10‐fold reduction in serum TxB2 formation; TxB2 generation by tumor cells was also significantly depressed. This treatment, however, did not significantly modify either primary tumor weight or metastasis formation. Our data suggest that selective inhibition of thromboxane generation in either blood or tumor cells does not prevent spontaneous metastasis formation in the murine model studied.
A highly leukemogenic radiation leukemia virus isolate is a thymotropic, immunosuppressive retrovirus with a unique rna structure
Authors: David Ya'acob Ben , Kotler Moshe , Yefenof Eitan
Published: February 2007

Clones of N‐, B‐ and NB‐fibrotropic viruses were isolated from weakly (D‐RadLV) and strongly (A‐RadLV) leukomogenic RadLV preparations. A highly leukemogenic, thymotropic virus (TV) was isolated by ex‐vivo infection of thymocytes with A‐RadLV. This virus could not be isolated from D‐RadLV. Two‐dimensional fingerprint analysis suggested that TV recombines unique RNA sequences with RNA genomic material derived from a B‐tropic endogenous virus. C57BL/6 (B6) mice injected with B‐ or NB‐fibrotropic clones, but not with TV or N‐tropic viral clones, developed reactive T lymphocytes (Tr), capable of differentiating into anti‐tumor cytotoxic cells. The N‐tropic virus isolates were non‐immunogenic in B6 mice whereas the TV isolate induced suppressor T lymphocytes (Ts) that abrogated a potential Tr response. These results suggest that emergence of highly leukemogenic RadLV involves activation of endogenous fibrotropic virus which is immunogenic in its natural host strain (B6). This virus can further recombine with other retroviral genetic sequences, resulting in a suppressogenic and thymotropic, highly leukemogenic virus.
Cultured mammary carcinoma cells contain gonadotropin‐releasing hormone‐like immunoreactivity, gnrh binding sites and chorionic gonadotropin
Authors: Bützow R. , Huhtaniemi I. , Clayton R. , Wahlström T. , Andersson L. C. , Seppälä M.
Published: February 2007

Immunoperoxidase staining and radioimmunoassay were used to identify gonadotropin‐releasing hormone (GnRH) and chorionic gonadotropin (hCG) in 4 mammary carcinoma cell lines. GnRH‐like immunoreactivity was found in all cell lines; 2 lines also contained hCG. Binding of a GnRH agonist was demonstrated by radioreceptor assay in cultured mammary carcinoma cells. In cell column perfusion of the same cells, exogenous GnRH did not stimulate release of hCG.
Establishment and characterization of a T‐lymphoblastoid cell line MDCC‐MTB1 derived from chick lymphocytes infected in vitro with marek's disease virus serotype 1
Authors: Ikuta Kazuyoshi , Nakajima Kazuhiro , Kanamori Akihiro , Maotani Kumiko , Mah Jum Sool , Ueda Shigeharu , Kato Shiro , Yoshida Mariko , Nii Shiro , Naito Matao , Nishida‐Umehara Chizuko , Sasaki Motomichi , Hirai Kanji
Published: February 2007

Continuously proliferating T‐lymphoblastoid cells, named MDCC‐MTB1, were obtained by infection of chick embryo lymphocytes with Marek's disease virus serotype 1 (MDV1) in culture and subsequent cultivation in the presence of human interleukin 2 (IL‐2). The MTB1 cells have now been growing well for at least 4 months with a doubling time of about 10 hr, irrespective of the presence of IL‐2. The MTB1 cells show lymphoblastoid morphology, and carry T‐lymphocyte marker surface antigens and a karyotype of female chick origin with several abnormal chromosomes. Southern blot hybridization showed that they contain about 10 virus genome equivalents/cell of almost the whole MDV genome. Infectious virus could not be rescued from MTB1 cells by co‐cultivation of these with chick embryo fibroblasts. In addition, no virus particles were found in thin‐sectioned MTB1 cells by electron microscopy. An immunofluorescence test with monoclonal antibody (MAb) to MDV‐specific phosphorylated proteins showed that MTB1 cells expressed the MDV‐specific antigen in the cytoplasm only after the cells had been treated with 5‐iodo‐2‐deoxyuridine for 48 hr at 41 °C. MTB1 cells can form colonies in 0.33% soft agar, and can be transplanted into chicks by i.p. injection. Thus, continuously growing lymphoblastoid cells were obtained by in vitro infection of chick embryo lymphocytes with oncogenic MDV1 and cultivation of the cells in the presence of human IL‐2 during the transformation step. These cells appear to show a similar phenotype to an MD lymphoma‐derived cell line.
Trisomy 15 as a regular finding in chemically induced murine t‐cell leukemogenesis
Authors: Carbonell F. , Eul J. , Anselstetter V. , Hameister H. , Seidel H. J. , Kreja L.
Published: February 2007

Trisomy 15 is described as a common finding in all T‐cell leukemias induced by a single dose of methylnitrosourea (MNU) in BDF1 mice and in the leukemias induced by 7 doses of benzo(a)pyrene. Additional trisomies were found in about half of the leukemias. The organ distribution suggests that the leukemic cells with trisomy 15 originate in the thymus. Trisomy 15 was detected in the thymus as early as 6 weeks after the application of MNU, i.e. during the latency period.
Aflatoxin exposure, hepatitis b virus infection and liver cancer in swaziland
Authors: Peers Frank , Bosch Xavier , Kaldor John , Linsell Allen , Pluijmen Mathieu
Published: February 2007

A study was carried out in Swaziland to assess the relationship between aflatoxin exposure, hepatitis B infection, and the incidence of liver‐cell carcinoma, which is the most commonly occurring malignancy among males in Swaziland. Levels of aflatoxin intake were evaluated in dietary samples from households across the country, and crop samples taken from representative farms. Prevalence of hepatitis B markers was estimated from the serum of blood donors, and liver cancer incidence was recorded for the years 1979–83 through a national system of cancer registration. Across 4 broad geographic regions, there was a more than 5‐fold variation in the estimated daily intake of aflatoxin, ranging from 3.1 to 17.5 μg. The proportion of HBV‐exposed individuals was very high (86% in men), but varied relatively little by geographic region; the prevalence of carriers of the surface antigen was 23% in men, and varied from 21 to 28%. Liver cancer incidence varied over a 5‐fold range, and was strongly associated with estimated levels of aflatoxin. In an analysis involving 10 smaller subregions, aflatoxin exposure emerged as a more important determinant of the variation in liver cancer incidence than the prevalence of hepatitis infection. Aflatoxin estimates from crop samples appeared to be a reasonable surrogate for dietary measurements. A comparison with dietary aflatoxin levels measured in an earlier survey in Swaziland suggested that programmes aimed at reducing contamination levels had had some success.
Second malignancies following testicular cancer, ovarian cancer and hodgkin's disease: An international collaborative study among cancer registries
Authors: Kaldor J. M. , Day N. E. , Band P. , Choi N. W. , Clarke E. A. , Coleman M. P. , Hakama M. , Koch M. , Langmark F. , Neal F. E. , Pettersson F. , Pompe‐Kirn V. , Prior P. , Storm H. H.
Published: February 2007

Eleven population‐based cancer registries tabulated second cancers among 133,411 patients diagnosed with testicular cancer, ovarian cancer or Hodgkin's disease between 1945 and 1984. Overall, 3,157 second cancers were observed, as compared with 2,420 expected at least one year after the first cancer. Survivors of testicular and ovarian cancer experienced 30% and 20% more cancers respectively than the general population comparison group, and patients previously diagnosed with Hodgkin's disease had an 80% excess of cancer. No information was available either on treatment for the first cancer, or other risk factors. However, temporal patterns in the risk of specific second cancers were analysed, with particular reference to the possible role of therapy for the first cancer. Leukaemia of the acute or non‐lymphatic type, which has been previously linked to alkylating agent therapy, occurred in excess following all 3 first cancers, as did non‐Hodgkin's lymphoma (overall relative risks of 6.1 and 1.8 respectively, with considerably higher relative risks following Hodgkin's disease). Other cancers for which important and plausibly therapy‐induced excesses occurred were lung cancer following Hodgkin's disease (relative risk 1.9), breast cancer following Hodgkin's disease (relative risk 1.4) and bladder cancer following ovarian cancer and Hodgkin's disease (relative risks 1.7 and 2.2 in women, respectively). Rarer sites at which striking excesses occurred were the salivary gland, thyroid, bone and connective tissue. There were smaller, but clear excesses for cancers of the rectum and colon following ovarian cancer and testicular cancer, skin cancer following Hodgkin's disease, and kidney cancer following ovarian cancer. Over‐diagnosis, misclassification of metastases and confounding by other risk factors were all considered as explanations of observed excesses. Nonetheless, it appeared that there are clear excess risks for cancers other than acute leukaemia which must be ascribed to therapy for the first cancer, especially in view of the possible under‐reporting in registry material. Case‐control studies are under way to provide information on the role of specific aspects of therapy.
The activation‐associated antigen 4f2 predicts patient survival in low‐grade b‐cell lymphomas
Authors: Holte Harald , Davies Catharina De L. , Kvaløy Stein , Smeland Erlend B. , Foss‐Abrahamsen Arne , Kaalhus Olav , Marton Per F. , Godal Tore
Published: February 2007

Expression of the activation‐associated 4F2 antigen, transferrin receptor and interleukin‐2 (IL‐2) receptor on suspended cells from 75 biopsied low‐grade non‐Hodgkin lymphomas (L‐NHL) of B‐cell origin was correlated to patient survival, clinical prognostic parameters and estimated DNA synthesis. 4F2 antigen expression correlated significantly with poor patient survival, high DNA synthesis and transferrin receptor expression. Transferrin receptor expression was associated with high DNA synthesis and treatment response, but not with patient survival. On the other hand, IL‐2 receptor was correlated neither to patient survival nor to other studied markers for cell activation, but seemed to be expressed on certain subsets of lymphomas. We suggest that monoclonal antibody (MAb) against the activation‐associated 4F2 antigen could be used to select patients with L‐NHL for aggressive chemotherapy.
Antibody protein dose and radioimmunodetection of gw‐39 human colon tumor xenografts
Authors: Sharkey Robert M. , Primus F. James , Goldenberg David M.
Published: February 2007

This study investigates the influence of antibody protein dose on the radioimmunodetection of a CEA‐producing, human colonic tumor xenograft (GW‐39) using affinity‐purified goat anti‐carcinoembryonic antigen (CEA) antibody and a murine monoclonal anti‐CEA antibody (NP‐2). Hamsters bearing GW‐39 tumors were given an equal mixture of 131I‐labelled antibody and 125l‐labelled irrelevant IgG at doses varying from 0.01 to 1.0 mg (0.1 to 10 mg/kg body weight) for each antibody preparation. No differences were found in the percentage of antibody in the tumor or the clearance rate from the blood as the antibody dose was increased. The concentration of antibody in the tumor increased proportionally with the antibody dose and maintained a linear relationship with increasing dose, indicating that antigenic sites in the tumor were not saturated with antibody. The concentration of irrelevant IgG in the tumor also increased proportionally as the dose was increased, but the concentration of irrelevant IgG in the tumor was less than the antibody and was removed more rapidly from the tumor than the antibody. By considering the amount of irrelevant IgG in the tumor as a measure of the amount of antibody non‐specifically bound, we determined that there was no change in the amount of antibody in the tumor between days 3 and 7, and the amount of antibody increased uniformly for both the tumor and non‐tumor tissues, resulting in no improvement in the tumor/non‐tumor ratios with increasing antibody dose. External scintigraphy verified that the dose of the antibody did not influence tumor imaging. Thus, tumor accretion of antibody in this model is not dependent principally on the antibody protein dose, and other factors such as accessibility to antigen and antibody metabolism may play important roles in regulating the uptake of antibody in tumor.
A new animal model for human colon cancer metastasis
Authors: Bresalier Robert S. , Raper Steven E. , Hujanen Erkki S. , Kim Young S.
Published: February 2007

An animal model for human colon cancer metastasis is described in which spontaneously metastasizing colonic tumors are formed after injection of human colon cancer cells into the cecal wall of young athymic nude mice. Lymphatic and vascular invasion were demonstrated histologically after injection of both well‐ and poorly‐differentiated cell lines, and metastases were found in a pattern similar to that of naturally occurring human colonic cancer. In contrast, little or no visceral organ involvement could be demonstrated after s.c. injection. Cells with increased liver‐metastasizing potential were obtained by serial selection in this system. These cells had an enhanced ability to penetrate a reconstituted basement membrane in the presence of partially purified liver extract when compared to lung or brain extracts in a modified Boyden chamber assay. These results demonstrate the ability of human epithelial tumor cells to metastasize reproducibly in an animal model system, which may be useful for studying many aspects of the pathogenesis of cancer metastasis. In addition, it is suggested that local invasion by colon cancer cells may be influenced in part by tissue‐specific factors.
W‐7, a calmodulin inhibitor, potentiates dacarbazine cytotoxicity in human neoplastic cells
Authors: Lönn Ulf , Lönn Sigrid
Published: February 2007

Dacarbazine induces damage in replicative DNA, with a maximum level at 24 hr after treatment. Repair of these lesions does not occur when cells are post‐treated with the calmodulin inhibitor W‐7. In parallel cell cytotoxicity increases. The augmentation effect of W‐7 is prevented by simultaneous incubation of cells with high levels of calmodulin and does not occur in cells pre‐treated with aphidicolin (to stop DNA synthesis). Furthermore, W‐5, an analogue of W‐7 with a less inhibitory effect on calmodulin, does not interfere with DNA repair. The results show that calmodulin and/or calmodulin‐regulated proteins are involved in the repair process of dacarbazine‐induced DNA lesions.
Lipomas have characteristic structural chromosomal rearrangements of 12q13‐q14
Authors: Mandahl N. , Heim S. , Johansson B. , Bennet K. , Mertens F. , Olsson G. , Rööser B. , Rydholm A. , Willén H. , Mitelman F.
Published: February 2007

Cytogenetic analysis was performed in 10 consecutive lipomas; 6 had typical benign histology whereas four had foci of atypia. Three tumors had supernumerary ring chromosomes, 6 had different balanced rearrangements, and one had a normal karyotype. Chromosome 12 was involved in 5 of the balanced rearrangements and, although less certainly, in all the ring chromosomes, with breakpoints localized to 12q13 or q14. The other rearranged chromosomes were numbers 2,3,7,8,11,17 and 22. These results demonstrate the non‐random involvement of chromosomal region 12q13‐q14 in benign lipogenic tumors. The combined data from this and previous studies on benign and malignant lipogenic tumors indicate that different levels of cytogenetic specificity exist within this group of neoplasms. We suggest that myxoid liposarcoma development requires the recombination of 2 specific chromosomal bands (12q13 and 16q11), whereas for some types of benign lipogenic tumors structural changes in 12q13‐q14 may be sufficient for neoplastic growth.
Glycoproteic nature of surface molecules of effector cells with lymphokine‐activated killer (LAK) activity. Evidence that T11, T8 or T3 molecules are not involved in tumor‐cell lysis by LAK effector T cells
Authors: Bagnasco Marcello , Mingari Maria Cristina , Pende Daniela , Venuti Daniela , Canonica Giorgio Walter , Moretta Lorenzo
Published: February 2007

Human peripheral blood mononuclear cells cultured in the presence of interleukin‐2 (IL‐2) acquire the capability of lysing NK‐resistant fresh tumor target cells. In an attempt to delineate the surface structure(s) present on the effector cells, the latter were first treated with different amounts of pronase and neuraminidase. The effect of the enzymes on cytolytic activity against fresh melanoma cells was evaluated and compared with the NK‐like activity against K562 target cells of the same effector population. At a pronase concentration of 0.01 mg/ml, no inhibition of NK‐like activity was detected, whereas LAK activity was inhibited by more than 75%. In addition, neuraminidase had no effect on NK‐like activity, even at I U/ml, whereas as little as 0.03 U/ml inhibited LAK activity by more than 75%. Metabolic inhibition of N‐linked glycosylation with Tunicamycin prevented the generation of LAK activity, even when added late (18 hr before termination of the culture). Tunicamycin, on the other hand, had no effect on the boost of NK activity induced by IL‐2. Provided that LAK activity can also be generated in T‐cell (E‐rosetting) populations, in the presence of adherent cells, we analyzed the inhibitory activity of monoclonal antibodies (MAbs) to T11, T3 and T8 molecules. While all these MAbs strongly inhibited the specific target cell lysis by alloreactive CTLs, they had no effect on the LAK activity.
Hot maté drinking and precancerous lesions of the oesophagus: An endoscopic survey in southern brazil
Authors: Muñoz Nubia , Victora Cesar G. , Crespi Massimo , Saul Carlos , Braga Noris M. , Correa Pelayo
Published: February 2007

Thermal injury resulting from drinking very hot beverages has been incriminated as a risk factor for oesophageal cancer, although no information is available on the lesions caused by this injury in human or experimental animals. The drinking of hot mate tea is very common in areas of moderately high incidence of oesophageal cancer in south‐eastern areas of South America. This study investigated the prevalence of precancerous lesions of the oesophagus in 60 unskilled male workers, of whom half were daily maté drinkers and the remainder were non‐maté drinkers. These 2 groups were matched for age, smoking and alcohol intake. Maté drinkers were 2.2 times more likely (p = 0.046) to develop histologically confirmed oesophagitis than non‐maté drinkers.
On the clonal origin of tumors: A review of experimental models
Authors: Iannaccone P. M. , Weinberg W. C. , Deamant F. D.
Published: February 2007

A number of current models of carcinogenesis postulate that rare events are critical in the formation of malignant neoplasms. The most fundamental prediction of the hypothesis that these events are rare is the clonality of neoplasms. Evidence from spontaneous neoplasms supports the contention that such neoplasms are clonal. However, there are a number of reasons to believe that spontaneous neoplasms are derived from large numbers of cells. The issue can be resolved with experimental cancer models. In order to determine whether experimentally induced neoplasms are derived from the clonal expansion of single cells, a variety of benign and malignant tumors can be induced in mosaic rodents. These animals comprise 2 genetically distinguishable cell lineages. If the neoplastic tissues obtained from mosaic animals are composed entirely of progeny of one or the other of the 2 cell lineages, it may be concluded that they are clonal. If, on the other hand, the neoplasms began from the proliferation of many cells, then neoplastic masses would be expected to contain cells of both lineages. The results from a number of these experiments have led to the conclusion that chemically induced neoplasms are clonal. Furthermore, malignant neoplasms are generally believed to develop in a stepwise manner. If they were derived from a single cell, then each of the stages leading to the formation of the cancer should be clonal. A variety of stages thought to be necessary precursors of cancer have been analyzed in mosaic rodents. These preneoplastic lesions have been determined to be clonal in origin. Thus, theories of carcinogenesis must account for the rarity of the events critical to the formation of cancer.
In vitro susceptibility of different human T‐cell subpopulations and resistance of large granular lymphocytes to HTLV‐I infection
Authors: Macchi B. , Popovic M. , Allavena P. , Ortaldo J. , Rossi P. , Gallo R. C. , Bonmassar E.
Published: February 2007

T4 subpopulation of T lymphocytes is the preferential target of infection with human T leukemia/lymphoma virus of subgroup I (HTLV‐I). In this study we attempt to determine whether different T‐cell subsets exbibit differences in susceptibility to virus infection. T cells from cord or peripheral blood were separated according to cell densities and T‐cell surface markers by Percoll gradient and Sepharose anti‐Fab immunoadsorbent affinity column (IAC), respectively. Separated T‐cell subpopulations were infected with HTLV‐I, by means of co‐cultivation with irradiated virus producer cell lines (MT‐2, TK). Percentages of HTLV‐I‐infected cells were assayed by immunofluorescence assay (IFA), using highly specific mouse monoclonal antibody (MAb) directed against HTLV‐I p19 core protein. The results showed that different T‐cell subpopulations separated either by Percoll or by IAC were susceptible to HTLV‐I infection with the exception of large granular lymphocytes (LGL), which exhibit high cell‐mediated natural cytotoxicity (CMNC). The susceptibility to HTLV‐I infection of T cells with CMNC activity was further studied on established cell clones with LGL morphology. The results showed again that these cells were resistant to the virus infection. The present studies indicate that different T‐cell subpopulations, irrespective of their size and of cell‐surface markers, are susceptible to HTLV‐I infection, with the exception of functionally mature LGL or of immortalized LGL clones.
Inhibition of murine lymphoma growth by adoptive transfer of lymphocytes sensitized to a xenogenized tumor variant
Authors: Bianchi R. , Romani L. , Puccetti P. , Fioretti M. C.
Published: February 2007

Lymphocytes immune to a highly immunogenic (“xenogenized”) variant of a murine lymphoma—which were shown to exert anti‐xenogenized tumor activity in a previously described model of tumor immunotherapy—were tested in the present study for possible suppressive effects on the growth of an i.c. graft of the original lymphoma. Remarkable tumor‐inhibitory effects followed the i.v. infusion of splenic lymphocytes sensitized or restimulated in vitro, or derived from animals immunized in vivo with the xenogenized tumor cells. The pattern of inhibition of the parental cells was apparently similar to that previously described for the xenogenized variant, but preliminary evidence suggests that the underlying mechanisms may be different.
The relationship of collagenolytic activity to stage of human colorectal carcinoma
Authors: Irimura Tatsuro , Yamori Takao , Bennett Stephen C. , Ota David M. , Cleary Karen R.
Published: February 2007

Collagenolytic enzymes produced by tumor cells are believed to play a significant role in the destruction of surrounding normal tissue and, in certain experimental animal systems, the ability of tumor cells to degrade type‐IV collagen (basement membrane collagen) correlates positively with those cells' metastatic capacity. We measured collagenolytic activity levels of extracts from freshly excised colorectal carcinoma tissues and of conditioned media from primary organ culture (total of 114 tissues from 53 patients) by using purified radio‐labelled type‐1 (rat tail) and type‐IV (mouse Engelbreth‐Holm‐ Swarm [EHS] sarcoma) collagens. Both type‐IV and type‐l collagenolytic activity levels of extracts from tumor and adjacent mucosa ranged from < I to 80 ng/hr/mg wet tissue, and no significant differences between mucosa and carcinoma tissues were observed. In conditioned media, the type‐IV collagenolytic activity was low for normal mucosa and benign tumors and slightly higher for carcinoma than for mucosa. In 5 of 32 primary tumors, collagenolytic activity levels were 2–5 times higher than in the rest of the tumors and mucosal tissues. There were no significant differences in collagenolytic activity levels of conditioned media and tissue extract from colorectal carcinoma of different Dukes' stages. Deep and superficial areas of primary tumors released similar type‐IV collagenolytic activity levels, suggesting that there was little intratumoral heterogeneity in the release of this enzyme.
Human tumor cell lines with pleiotropic drug resistance are efficiently killed by interleukin‐2 activated killer cells and by activated monocytes
Authors: Allavena P. , Grandi M. , D'Incalci M. , Geri O. , Giuliani F. C. , Mantovani A.
Published: February 2007

Two human cell lines, the colon carcinoma Lovo and the transformed intestinal 1–407, and their variants (Lovo/Dx and l‐407/Dx), with pleiotropic resistance to cancer chemothera‐peutic drugs, were examined for their susceptibility to human lnterleukin‐2‐activated killer cells and to activated mono‐cytes. These non‐specific or broadly specific effector cells expressed cytotoxicity levels on pleiotropically resistant tumor cells comparable to those of the parental cell populations. This finding provides a rationale for immunological approaches designed to eradicate residual tumor cells surviving and resistant to cytotoxic chemotherapy.
Monoclonal integration of HTLV‐I proviral DNA in patients with strongyloidiasis
Authors: Nakada K. , Yamaguchi K. , Furugen S. , Nakasone T. , Nakasone K. , Oshiro Y. , Kohakura M. , Hinuma Y. , Seiki M. , Yoshida M. , Matutes E. , Catovsky D. , Ishii T. , Takatsuki K.
Published: February 2007

The relationship between strongyloidiasis and HTLV‐I was investigated in Okinawa, an area where both conditions are endemic. Thirty‐six patients with strongyloidiasis were sero‐positive for HTLV‐I and suffered from several related clinical complications. Fourteen of these patients (39%) were shown to have monoclonal integration of HTLV‐I proviral DNA in their blood lymphocytes, a condition designated as “smouldering” adult T‐cell leukaemia (ATL). Monoclonal integration of proviral DNA correlated with an increased CD4/CD8 ratio and the presence of abnormal lymphocytes in the peripheral blood, and with a trend for greater severity of the parasitic infection. Although the immunodeficiency caused by HTLV‐I could predispose to hyper infestation by Strongyloides, it is also possible that both the parasitic and the retroviral infestations are important co‐factors leading to the development of ATL.
Clonal rearrangements of T‐cell receptor and immunoglobulin genes and immunophenotypic antigen expression in different subclasses of Hodgkin's disease
Authors: Griesser Henrik , Feller Alfred C. , Mak Tak W. , Lennert Karl
Published: February 2007

Twenty‐two cases of Hodgkin's disease (HD), representing the 4 different subclasses, were studied by immunophenotypic and immunogenotypic analysis. Quantitative immunophenotypic analysis of HD infiltrates showed a predominance of CD3‐positive T cells in all subtypes except the lymphocytic depletion (HDLD) subtype. Only 5 samples of HD [2 of lymphocytic predominance (HDLP), 2 of mixed cellularity (HDMC), and one of nodular sclerosis type (HDNS)] were found to have both their Ig and T‐cell antigen receptor (TcR) genes in the germ‐line configuration. The remaining patients with HDLP (3 cases), HDNS (5 cases), and HDMC (4 cases), all exhibited rearrangements of either TcRγ or TCRγ and TcRβ genes, while all 5 cases of HDLD had either TCRγ or immunoglobulin heavy‐chain gene rearrangement. These results substantiate the view that Hodgkin's lymphomas contain clonal lymphocyte populations and that different rearrangement patterns may be associated with different subclasses of HD.
Trends in incidence of ocular malignant melanoma in Denmark 1943–1982
Authors: Østerlind Anne
Published: February 2007

All records of ocular malignant melanoma notified to the Danish Cancer Registry between 1943 and 1982 were re‐coded, and 1,624 out of 1,650 cases were verified and included in this investigation. The annual number of incident cases increased from about 30 to 50, but the age‐standardized incidence rate remained stable at 0.75 per 100,000 in males and 0.60 In females. There was no predilection for one or the other eye in either sex. About 80% of the tumours were located in the choroid, 10% in the ciliary body and iris, 5% in the conjunctiva, and 5% in “multiple regions”. The histopathology of the tumours was: epithelioid cell type in 12%, spindle‐cell type in 36%, and mixed‐cell type in 51%. The stable incidence rates of ocular malignant melanomas were in marked contrast to the 5‐to 6‐fold increase observed for cutaneous melanomas during the same time period. Possible differences in risk factors are discussed. Similarities and differences between the present data and results from other countries are highlighted.
Autologous mixed lymphocyte‐tumor reaction and autologous mixed lymphocyte reaction. I. Proliferation of two distinct T‐cell subsets
Authors: Uchida Atsushi , Moore Michael , Klein Eva
Published: February 2007

In patients with carcinomatous pleural effusions blood T lymphocytes proliferated in vitro in response to autologous, freshly isolated effusion tumor cells in the autologous mixed lymphocyte‐tumor culture (AMLTC) and to autologous blood non‐T cells in the autologous mixed lymphocyte culture (AMLC). Treatment of the stimulator cells with the anti‐HLA‐DR monoclonal antibody (MAb) abrogated the stimulatory capacity in AMLC, but not in AMLTC. A subset of T cells that formed rosettes with autologous erythrocytes showed proliferative response to autologous non‐malignant cells, whereas this subset did not respond to autologous tumor cells. Non‐adherent lymphocytes were fractionated by centrifugation on discontinuous Percoll density gradients. Medium‐sized T lymphocytes were excellent responders in AMLC, but were weak responders in AMLTC. Small T lymphocytes proliferated preferentially in AMLTC, but responded poorly in AMLC. Large granular lymphocytes (LGL) did not proliferate in mixed cultures of either type. Instead, LGL suppressed the T‐cell proliferation in AMLTC. The same suppressor LGL, however, had no inhibitory effect on AMLC. Elimination of the CD4 subset reduced or abolished proliferative response in AMLC in all cases, whereas it was ineffective in diminishing the reaction in 6 of 8 AMLTC. In contrast, removal of the CD8 subset decreased or eliminated T‐cell proliferation in 4 of 8 AMLTC, but in none of the AMLC. These results indicate that the auto reactive T lymphocytes detectable in response to tumor cells and non‐malignant non‐T cells differ in several characteristics. Thus, the reaction in the AMLTC is not due to contaminating non‐malignant cells in the stimulator population and may be a tumor‐induced prolixferative response.
Aberrant ribonucleotide pattern in lymphoid cells from patients with chronic lymphocytic leukaemia or non‐Hodgkin lymphoma
Authors: De Korte Dirk , Haverkort Willem A. , Roos Dirk , Van Gennip Albert H.
Published: February 2007

The intracellular purine and pyrimidine ribonucleotide concentrations were determined in lymphoid cells from peripheral blood of 16 patients with chronic lymphocytic leukaemia (CLL) and from peripheral blood and/or lymphoid tissue of 18 patients with non‐Hodgkin lymphoma (NHL). Compared to normal peripheral lymphocytes, the lymhoid cells from CLL patients contained lower, and those from NHL patients higher amounts of nucleotides. The lymphoid cells of NHL patients showed an imbalance in the nucleotide pool compared to either normal resting peripheral or proliferating tonsillar lymphocytes. The lymphoid cells of patients with CLL showed an imbalance only when compared to normal, resting peripheral lymphocytes. The abnormalities in the nucleotide pools involved decreased ratios of purine:pyrimidine, adenine:guanine and uracil:cytosine nucleotides. Lymphocytes from CLL and NHL patients contained increased amounts (relative and/or absolute) of UDP sugars, and NHL lymphocytes also showed a changed composition of the UDP sugars. Analysis of the ribonucleotides in the lymphoid cells provides useful information for the differential diagnosis of patients suspected of having CLL or NHL, and may be valuable for the design of new chemotherapeutic regimens.
Conversion of the lymphoma line “BJAB” by Epstein‐Barr virus into phenotypically altered sublines is accompanied by increased C‐myc mRNA levels
Authors: Wennborg Anders , Åman Pierre , Saranath Dhananjaya , Pear Warren , Sümegi Janos , Klein George
Published: February 2007

The steady‐state level of c‐myc proto‐oncogene mRNA was investigated in the EBV‐negative human B‐lymphoma line BJAB and 2 sublines that have been converted by EBV into stable EBV‐genome‐carrying and EBNA‐positive status. The EBV‐converted sublines expressed c‐myc at a 2‐to 6‐fold higher level than the original BJAB during exponential growth. The EBV‐positive BJAB lines are known to differ from the parent line in several phenotypic characteristics, including increased agarose clonability, lower serum requirements and, in one case, increased tumorigenicity in nude mice. The pattern of increased c‐myc expression accompanying EBV conversion was not observed in the myc/lg translocation‐carrying Burkitt lymphoma line RAMOS or in 2 of its EBV‐converted sublines.
Differential effects of retinoic acid on the in vitro growth and cell‐surface glycoconjugates of 2 human head and neck squamous‐cell carcinomas
Authors: Lotan Reuben , Sacks Peter G. , Lotan Dafna , Hong Waun K.
Published: February 2007

As a part of an assessment of the potential use of retinoids in preventive and adjuvant treatment of HNSCC, we examined the effects of β‐all‐trans retinoic acid (RA) on the growth and cell‐surface glycoconjugates of 2 HNSCC cell lines. These lines, designated 1483 and 183A, were established from an untreated patient with a well‐differentiated SCC of the re‐tromolar trigone and one with a poorly differentiated SCC of the tonsil. Whereas the 1483 cells were sensitive to RA in that their anchorage‐dependent growth, their colony growth on solid substratum, and their anchorage‐independent growth in semi‐solid agarose gel were all inhibited in a dose‐dependent fashion by RA concentrations in the range between I nM and 10 μM, the 183A cells were not inhibited by RA. Their anchorage‐dependent growth and colony formation were stimulated by RA, whereas their anchorage‐dependent colony formation was not altered. Cell‐surface glycoconjugates were modulated by RA in the sensitive 1483 cells but not in the 183A cells. Treatment of the 1483 cells resulted in a large increase in the cell‐surface labelling of high‐molecular‐weight (Mr > 400,000) galactoglycoconjugates and sialoglycoconjugates, as well as an Mr 280,000 sialoglycoconjugate. Glycoconjugates with similar electrophoretic mobilities in polyacrylamide gels were labelled intensely on the surface of the 183A cells even before RA treatment and only minor changes were noticed in their labelling after treatment. These results demonstrate that RA can exert different effects on different HNSCC lines, and suggest that correlations might exist between responsiveness to RA and the stage of differentiation of the HNSCC, and between modulation of cell growth and enhancement of cell‐surface glycoconjugate glycosylation by RA.