bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural antibodies to cell‐surface antigens of human astrocytoma
Authors: Pfreundschuh M. , Röhrich M. , Piotrowski W. , Berlit P. , Penzholz H.
Published: February 2007

Sera of 200 non‐transfused healthy male blood donors were tested for antibody reactivity to cell‐surface antigens of cultured astrocytoma cells. Positive reactions were observed only rarely by protein‐A assay (PA), in about half the cases by immune adherence assay (IA) and in nearly all cases by anti‐C3 mixed hemadsorption assay (C3‐MHA). In general, titers were low and only seven sera showed reactivity at 1:1,000. Serum 537 showed the strongest reaction. The anti‐astrocytoma reactivity in this serum was due to an IgG antibody. Extensive absorption analysis with a panel of cell lines and fresh cells of both benign and malignant origin, as well al fetal cells, revealed that this serum detected an anigen that was present on most neural‐crest‐derived tumors (astrocytomas, melanomas and neuroblastomas), on very few other malignant tumors and on fetal brain. The antigen detected by serum 537 shows close relationship to the astrocytoma antigen Aj which had been defined by the serum of a patient with astrocytoma. Both antigens appear to be differentiation antigens present predominantly on non‐epithelial neoplasms. The antigen detected by serum 537 is heat‐stable and pronase‐resistant. The sera of two other healthy donors apparently had a similar specificity, whereas the four other high‐titered sera and all other sera detected class‐III antigens which were non‐specific and not tumorrestricted.
Colony growth and chemosensitivity in vitro of human melanoma biopsies. relationship to clinical parameters
Authors: Tveit Kjell M. , Fodstad Øystein , Lotsberg Jostein , Vaage Sigmund , Pihl Alexander
Published: February 2007

To study the usefulness of an in vitro colony‐forming assay in predicting individual clinical responses to chemotherapy, tumor cells obtained from 150 melanoma metastases (119 patients) were grown in soft agar according to the method of Courtenay and Mills (1978), and tested for sensitivity to DTIC, CCNU, vinblastine, procarbazine, abrin and ricin. In 83% of the cases colony formation was observed (plating efficiency, PE, greater than 0.01%). Twenty‐seven per cent of the tumors gave PEs ⪖1%, 45% gave PEs in the range 0.1‐0.9%, whereas 11% of the tumors gave 0.01‐0.09%. The PEs were not correlated with the degree of pigmentation or with the clinical course. Evaluable chemosensitivity data were obtained on 104 metastases from 83 patients. Large differences in sensitivity were seen. In cases which were evaluable both in vivo and in vitro a clear correlation was found between the in vitro chemosensitivity, expressed as the expected growth delay, and the clinical response to chemotherapy. Tumors from patients with partial response, mixed response or stable disease after prior progression, all had rather high in vitro sensitivity to the drug used (expected growth delay ⪖2.0), whereas patients with progression had lower sensitivity. The results confirm that the soft agar method used here provides good culture conditions for human melanoma cells and show that chemosensitivity data can be obtained in a high percentage of melanoma patients. The approach used seems promising in aiding clinicians to adjust chemotherapy to individual patients.
Specificity of auto‐tumor cytotoxicity exerted by fresh, activated and propagated human t lymphocytes
Authors: Vánky Farkas , Klein Eva
Published: February 2007

The specificity of auto‐tumor cytotoxicity exerted by patients' T lymphocytes was investigated. Lymphocytes, both activated and non‐activated, were used as effectors against freshly separated tumor cells. Activation was achieved by treatment with interferon (Hu‐IFN‐α), stimulation with PHA, co‐cultivation with autologous tumor biopsy cells (ATS) and allogeneic lymphocytes (MLC). Of these activation systems, ATS was the most efficient in generating auto‐tumor cytotoxicity. In some cases the lymphocytes activated in MLC or treated with PHA also damaged autologous tumor cells, but IFN‐pretreatment of the lymphocytes had no such effect. When the ATS‐ or MLC‐activated lymphocytes were propagated with conditioned medium known to contain Interleukin‐2, their lytic potential against autologous tumors was maintained. In addition to autologous tumor biopsy cells, the effector populations were also confronted with other targets such as Con A blasts and allogeneic tumor biopsy cells. The latter were lysed by the lymphocytes activated in MLC, but not by the ATS cultures. Thus, on the population level, the ATS was specific for the autologous tumor cells. Cold target competition tests suggested that in the MLC‐s the autologous tumor cells were killed by a distinct set of lymphocytes because allogeneic cells (tumor cells or the stimulator lymphocytes), even if killed by the same effector populations, did not compete. Thus, in these cultures the auto‐tumor specificity of the lysis was on the level of the effector subset. Therefore, it is likely that, independently of the mode of activation, the auto‐tumor lysis is the function of lymphocytes which recognize tumor‐ or organ‐specific antigens on the target cells.
Organotropism of the lymphoproliferative disease virus (lpdv) of turkeys
Authors: Gazit Arnona , Schwarzbard Zivia , Yantv Abraham , Ianconescu Marius , Perk Kalman , Zimber Amatzia
Published: February 2007

Turkey poults were inoculated with lymphoproliferative disease virus (LPDV) of turkey, and the organotropism of the inoculated virus was determined from the kinetics of virus expression and tumor formation. Molecular hybridization experiments, conducted to determine the level of viral RNA expression in the various organs of infected birds, established lymphoid tissues, including bone marrow, as the target for LPDV infection. Of these, bone marrow was the first to be infected but subsequently virus replication extended to the thymus, the spleen and the bursa of Fabricius. The low level of LPDV expression in non‐target organs probably stemmed from infiltration of infected lymphatic cells. The fact that the main organs for virus replication were not invariably the ones most clinically involved suggests that the target cells for virus infection need not necessarily be the targets for virus oncogenicity. A possible mode for LPDV infection and transformation is proposed.
Sister chromatid differentiation and cell‐cycle‐specific patterns in chronic myelocytic leukemia and normal bone marrow
Authors: Becher Reinhard , Schmidt Carl G.
Published: February 2007

After In vitro incubation with bromodeoxyuridine (BrdUrd)‐containing medium, metaphases of Philadelphia (Ph<1>)‐chromosome positive cells in the blood and/or bone marrow of eight untreated patients with chronic myelocytic leukemia (CML) were analysed by means of sister chromatid differentiation (SCD) and compared to 10 normal bone marrows. The majority of proliferating Ph<1>‐positive cells (range: 46‐86%) were unable to complete more than one cell cycle during the culture period of 50 h (M1 metaphases). Ph<1>‐positive M2 metaphases which had completed two cell cycles were found in the range of 18‐54% and almost no M3 metaphases were detected after passage through three cell cycles (0‐1%). The corresponding findings in proliferating normal bone‐marrow cells were: M1 (13‐68%), M2 (30‐79%) and M3 (0‐18%). These data support the notion that there is a prolonged cell cycle time in CML which can be measured by SCD, demonstrating a proportional shift from M3/M2 to M1 metaphases. SCD is suggested for kinetic studies on human malignant cell clones characterized by marker chromosomes.
HLA complex and familial malignant melanoma
Authors: Pellegris Giuseppe , Illeni Maria Teresa , Rovini Dario , Vaglini Maurizio , Cascinelli Natale , Ghidoni Achille
Published: February 2007

Six families with familial malignant melanoma (FMM) were HLA‐A, ‐B, and ‐C typed to ascertain whether or not FMM would segregate with the HLA complex. The HLA‐B12 antigen was present in five of the six families. In three families the HLA‐FMM linkage could be analyzed: linkage was possible in two but not in the third. These findings suggested that two types of FMM may exist: a more frequent type (five cases) that apparently segregates with the HLA complex and another (one case) that does not segregate with the HLA complex. Moreover, a factor included in the HLA region or another factor linked to it may have played an important role, in five of the six families, in FMM pathogenesis, whereas in the sixth family its role may have been performed by some other factor. These findings are consistent with the hypothesis of two complementary factors (one of which was included in the HLA complex) for the promotion of FMM with dominant inheritance and high penetrance.
Human large‐bowel cancer: Correlation of clinical and histopathological features with banded chromosomes
Authors: Reichmann Amelia , Levin Bernard , Martin Paulette
Published: February 2007

Clinical and histopathological features were correlated with cytogenetic banding studies on direct preparations from 31 large‐bowel tumors. An interesting relationship between the site and the karyotypes of the tumors was observed. There appears to be a progressive increase in chromosomal number and/or structural rearrangement as one progresses from proximal to distal large bowel. We suggest that these observations may be related to differences in function and micro‐environment within different areas of the colon. Although it is not known what factors favor cytogenetic variability and instability on the left side or the presence of fewer abnormalities on the right side of the colon, it is evident that clonal karyotypic evolution may be important in the progression of large‐bowel cancer. The brevity of follow‐up precludes conclusions regarding the influence of karyotype on survival.
Antibodies to adult t‐cell leukemia‐virus‐associated antigen (atla) in sera from patients with atl and controls in japan: A nation‐wide sero‐epidemiologic study
Authors: Hinuma Y. , Komoda Haruko , Chosa T. , Kondo T. , Kohakura M. , Takenaka T. , Kikuchi M. , Ichimaru M. , Yunoki K. , Sato I. , Matsuo R. , Takiuchi Yasuko , Uchino H. , Hanaoka M.
Published: February 2007

A nation‐wide sero‐epidemiologic survey of adult T‐cell leukemia virus (ATLV), detected es anti‐ATLA (ATLV‐associated antigen), was made in Japan. Sera from adult donors in 15 different locations were screened for anti‐ATLA. High incidences (6 to 37%) of antibody‐positive donors were found in seven regions, one in northern Japan, and the others in southwestern regions. These areas are ATLV‐endemic areas corresponding to ATL‐endemic areas. Examination of sera from healthy donors aged 6 to 80 years in ATL‐endemic areas showed an age‐dependent increase of seropositive donors with a maximum of about 30% at 40 years of age. Anti‐ATLA was found in all but two of 142 patients with ATL Anti‐ATLA‐positive patients with ATL were mainly found in ATLV‐endemic areas, and only a few in ATL‐nonendemic areas. Six patients with cutaneous T‐cell lymphoma in ATLV‐nonendemic areas gave a negative reaction for anti‐ATLA. The geometric mean titer of anti‐ATLA of patients with ATL was higher than that of healthy donors.
Socio‐economic class differences in cancer incidence in cali, Colombia
Authors: Cuello Carlos , Correa Pelayo , Haenszel William
Published: February 2007

Based on census tract information, cancer incidence rates for three socio‐economic strata of the city of Cali, Colombia, were calculated. Strong negative associations with socio‐economic status were found for cancers of the cervix and stomach. Colon cancer and endocrine‐related cancers were positively associated with socio‐economic status, while no such association was found for rectal cancer. Contrary to data from developed countries, all smoking‐related cancers were positively associated with socio‐economic class. The role of socio‐economic gradients in developing countries is stressed as a basis for etiological research.
Reactivity with patient antibodies of partially purified gp40 antigen from immune complexes in burkitt's lymphoma and nasopharyngeal carcinoma
Authors: Gazitt Y. , Klein G. , Sultzeanu D.
Published: February 2007

A glycoprotein antigen (gp40) was previously identified as a major component of immune complexes isolated from sera of patients with Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC). In the present work gp40 was partially purified from a pool of BL/NPC sera. Sera of patients with BL and NPC as well as sera of patients with other malignant and non‐malignant diseases were tested for antibodies against gp40, using a double antibody radioimmunoassay. Practically all normal sera and sera of patients with non‐malignant diseases had antibodies capable of binding radioiodinated gp40. In contrast, sera of patients with BL or NPC had very low binding, while sera of patients with other malignant diseases had intermediate binding values. The low binding activity of BL/NPC sera was shown to be due to inhibition by excess gp40 present in such sera. Effusions of patients with breast or ovarian cancer also contained demonstrable amounts of gp40. The origin of gp40 is still unknown.
Shut‐down of virus synthesis during progression of erythroleukemia induced by friend virus in mice
Authors: Yoosook Chalobon
Published: February 2007

Infection of (C57BL/6 × DBA/2)F1 (BDF1) mice with 2,500 FFU of Friend virus complex (FV) resulted in erythroleukemia followed by recovery, at which time virus could not be detected in the spleens of mice, and with splenomegaly (progressor mice) or without splenomegaly (regressor mice). Progressor and regressor mice developed equally high amounts of FV‐neutralizing activity in their sera. Progressor mice contained cells capable of producing virus, despite the lack of viral envelope antigen(s) in their spleens. The tropism of FV recoverable from the spleens of secondary recipients, injected with spleen cells from progressor mice, did not show any change, although the viral genome was present in Fv‐I‐restrictive host for at least 7 weeks. When the number of spleen colony‐generating cells was enumerated, by the spleen colony assay, the frequency in normal syngeneic and in allogeneic hosts was approximately the same at the early stage of erythroleukemia but was about 1,000 times higher in the syngeneic recipients during leukemia progression. These spleen colony‐generating cells were considered to be FV‐transformed cells capable of self‐renewal and capable of generating infectious centers (IC), respectively. Most of these transformed cells might be non‐producer leukemia cells.
CLONAL NATURE OF SPONTANEOUS AKR LEUKEMIA: STUDIES UTILIZING THE X‐LINKED ENZYME PHOSPHOGLYCERATE KINASE
Authors: Collins Steven J. , Fialkow Philip J.
Published: February 2007

AKR mice heterozygous at the X‐linked phosphoglycerate kinase (PGK) locus were used in experiments to determine the number of cells from which spontaneous thymic leukemias (thymomas) develop. Because only one of the two X‐chromosomes is active in XX somatic cells, thymic leukemias that are clonal should display either type A or type B PGK, but not both, while those that are multicellular in origin may exhibit both enzymes. Spontaneous thymomas from 19 PGK heterozygous animals expressed exclusively (I I tumors) or predominantly (8 tumors) a single enzyme in contrast to non‐malignant tissue from these animals which expressed both enzyme types in approximately equal ratios. When primary tumors expressing a single or predominant enzyme type were transplanted, the transplanted tumors invariably displayed the PGK phenotype that predominated in the initial tumor indicating that the minor PGK component was not contributed by malignant cells. These results indicate that spontaneous AKR leukemias are clonal.
Detection of tumor antigens by syngeneic antiserum on in vitro, transformed tracheal epithelial cell line 2‐10‐1
Authors: Braslawsky G. R. , Kennel S. J. , Steele V. , Nettesheim P.
Published: February 2007

Sera obtained from rats showing transplantation immunity to syngeneic, malignant epithelial cell line, 2‐10‐1, were used to identify antigens associated with transformation in vitro. The 2‐10‐1 cell line was derived from exposure of tracheal explants, in vitro, to the carcinogen MNNG. Tumorigenic passages of the cell line were shown to have common antigenic determinants, shared by independently transformed malignant tracheal epithelial cell lines, as well as antigenic determinants that appear to be limited to the immunizing cell line, 2‐10‐1. Care was taken to ensure that antibodies were not produced against viral antigens or non‐specifically absorbed serum components. Early passages of the 2‐10‐1 cell line were not tumorigenic in athymic BALB/c (nu/nu) mice, but became malignant with serial passage in vitro. Antigenic specificities recognized by 2‐10‐1 immune sera were also present on earlypassage 2‐10‐1 cells that had not as yet acquired the malignant phenotype. Such antigen expression must be an early event in neoplastic development.
Corynebacterium parvum prevents immunization to admixed irradiated tumor cells by a local process
Authors: Titus Michael J. , Bartlett Gerald L. , Kreider John W.
Published: February 2007

Immunization of mice with 106 irradiated LSTRA murine leukemia cells (LX) induced weak immunity to subsequent tumor‐cell challenge. Admixture of low doses (1.4‐14 μg) of C. parvum with the LX usually augmented the immunity. Higher doses (1,400‐7,000 μg) of admixed C. parvum not only failed to augment immunity, but prevented immunization by the contained LX. We investigated the mechanism by which 1,400 μg of C. parvum mixed with 106 LX prevents immunization by the LX. The inhibitory effect was a function of the ratio of C. parvum to tumor cells. Injection of 1,400 μg C. parvum, alone or mixed with the LX, did not prevent immunization by LX given simultaneously at a separate site. Injection of C. parvum, alone or mixed with the LX, did not prevent immunization by LX injected simultaneously at a separate site sharing a common lymph‐node drainage area. The high dose of C. parvum prolonged retention of radiolabelled LX at the injection site and decreased the rate of distribution of the LX to other organs, particularly the spleen. These results indicate that a high dose of C. parvum prevented immunization through a localized process at the injection site.
Effect of selenium on the induction of breast fibroadenomas by adenovirus type 9 and 1,2‐dimethylhydrazine‐induced bowel carcinogenesis in rats
Authors: Ankerst Jaro , Sjögren Hans O.
Published: February 2007

Selenium in its organic and inorganic forms has been shown to inhibit the development of chemically induced, spontaneous and transplanted tumors. The present investigation was performed to study the effect of selenium (4 μg per ml of drinking water) on tumorigenesis of adenovirus‐type‐9‐induced breast fibroadenomas and on 1,2‐dimethylhydrazine‐induced bowel carcinogenesis in WF rats. It was found that identical treatment with Se under identical conditions and with no obvious toxic effects on the rats (I) resulted in inhibition of DMH‐induced large‐bowel carcinogenesis; (2) facilitated induction of small‐bowel cancer by the same carcinogen in the same animals, and (3) greatly facilitated induction of breast fibroadenoma by adenovirus type 9 in the same strain of rats. The effect of Se treatment on DMH‐induced largebowel carcinogenesis confirms previous findings and proves that the opposite effect on fibroadenoma development is not due to differences in e.g. effective dose, animal strains or condition of the animals. It is not yet clear through which mechanisms Se exerts these effects.
Cancers of the digestive tract, alcohol and tobacco
Authors: Turns A. J. , Péqljignot G. , Gignoux M. , Valla A
Published: February 2007

In a systematic search for risks associated with the consumption of alcohol and tobacco in relation to cancers of the digestive tract, oesophageal cancer was found to be significantly related to both factors. There was a slightly elevated risk for rectal cancer among alcohol consumers as well as a lower risk for gastric cancer. With the exception of oesophageal cancer, none of the other digestive tract cancers were found to be associated with tobacco consumption.
Abnormal sensitivity to UV‐radiation in cultured skin ibroblasts from patients with hereditary cutaneous malignant melanoma and dysplastic nevus syndrome
Authors: Smith Paul J. , Greene Mark H. , Devlin Deborah A. , McKeen Elisabeth A. , Paterson Malcolm C.
Published: February 2007

The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). Although environmental exposures, especially solar UV‐irradiation, have been implicated as risk factors in sporadic melanoma, the role of such exposures in the pathogenesis of HCMM is unknown. We have studied the in vitro radiation responses of six non‐tumor skin fibroblast strains from HCMM/DNS patients representing five families. All six HCMM/DNS strains were found to show some degree of enhanced cell killing sensitivity, compared with normal controls, following 254 nm UV‐irradiation. The abnormal survival responses appeared to relate to specific characteristics of HCMM/DNS cells since the six strains had essentially normal sensitivity to γ‐radiation. The enhanced photosensitivity was not associated with abnormal patterns in either DNA repair synthesis or UV‐induced inhibition and recovery of de novo DNA synthesis. The survival results are consistent with the hypothesis that the genetically determined predisposition to malignant melanoma may directly or indirectly be the consequence of increased susceptibility to UV‐induced cellular damage.
Detection of polyoma‐virus‐induced tumor antigen(S) by macrophage migration inhibition
Authors: Szigeti Robert , Dalianis Tina , Klein George , Ito Yoshiaki , Magnusson Göran
Published: February 2007

We have applied the macrophage migration inhibition assay to study cell‐mediated immune responses to antigens of polyoma‐virus‐transformed cells. Macrophages from polyoma‐virus‐immunized mice, but not from control mice, showed significant migration inhibition when exposed to extracts of polyoma‐virus‐induced mouse and rat transformed cells. Extracts of non‐polyoma‐induced tumors had no such effect.
Role of NK cells in the control of metastatic spread and growth of tumor cells in mice
Authors: Gorelik E. , Wiltrout R. H. , Okumura K. , Habu S. , Herberman R. B.
Published: February 2007

The ability of BALB/c nude and C57BL/6 mice to eliminate tumor cells from the blood stream was severely impaired after a single inoculation of 0.2 ml of anti‐asialo BMI (asGMI) serum, diluted 1:40 to 1:320. The number of i.v.‐inoculated YAC‐I cells surviving in the lungs of BALB/c nude mice pretreated with anti‐asGMI serum was 28 times higher than in the control nude mice. In this respect, nude mice treated with anti‐asGMI behaved similarly to beige mice. The increase in the initial survival of tumor cells in the mice that was induced by pre‐treatment with anti‐asGMI resulted in a substantial increase in the number of artificial lung metastases that developed. In C57BL/6 +/+ mice treated with anti‐asGMI and in C57BL/6 beige mice, i.v. inoculation of B16 melanoma cells induced 10 times more metastatic foci in the lungs than in the control C57BL/6 +/+ mice. In contrast, in nude mice which possess higher levels of NK reactivity, metastatic growth was suppressed 7‐fold in comparison with intact C57BL/6 +/+ mice. In beige mice and in C57BL/6 +/+ mice treated with anti‐asGMI, multiple metastatic foci developed in the liver, whereas in control C57BL/6 +/+ and nude mice, no extrapulmonary metastases were found. These data indicate that B16 melanoma cells are able to grow in the liver, but their growth is ordinarily prevented by NK cells. The antimetastatic defense of C57BL/6 mice treated by anti‐asGMI could be restored by transplantation of 40 × 106 normal spleen cells. This antimetastatic effect of transplanted spleen cells was mediated by asGMI‐bearing cells, since after in vitro pre‐treatment of normal spleen cells with anti‐asGMI and complement, they lost their ability to inhibit the development of artifical metastases in the lungs of C57BL/6 mice. Suppression of NK reactivity by multiple injections of anti‐asGMI (every 4 to 5 days), in C57BL/6 mice inoculated intrafootpad (i.f.p.) with B16 melanoma or 3LL tumor cells, did not influence the growth of local tumors, but dramatically accelerated the development of spontaneous pulmonary metastases. These data demonstrate that NK cells may play an important role in resistance to the dissemination of tumor cells, and therefore contribute to the control of metastasis formation in mice.
Quantitation of proliferative and cytotoxic precursor cells directed against human tumours: Limiting dilution analysis in peripheral blood and at the tumour site
Authors: Vose Brent M.
Published: February 2007

Blood and tumour‐infiltrating lymphocytes (TIL) from 16 cancer patients have been examined under limiting dilution conditions to determine the frequency of cells responding in mixed tumour‐lymphocyte cultures (MLTC) to autologous tumour and Interleukin‐2 (IL‐2). Tumour‐derived lymphocytes showed a high spontaneous response to IL‐2 alone 1/1,900 in TIL; 1/6,000 in PBL suggesting the presence of “activated” T cells in situ. Proliferative frequencies were increased in MLTC in both blood (1/3,779) and TIL (1/1,084). Phenotypic analyses showed that total T‐cell contents of the responder populations were comparable but TIL were enriched for the OKT8+ subset with a corresponding reduction in OKT4+. TIL showed increased numbers of OKMI+ and Tac+ lymphocytes. The major cytotoxic precursor expanding under these conditions was reactive against autologous tumour. K562 (NK) were present at a lesser frequency ‐particularly in TIL The data show a concentration and activation of reactive lymphocytes at the tumour site and establish conditions for the clonal expansion of specifically cytotoxck T cells.
Establishment and cytological characteristics of two in vitro T‐cell lines derived from a child with acute lymphatic leukemia and a man with adult T‐cell leukemia in Japan
Authors: Nagasaka Miharu , Maeda Sakan , Mabuchi Osamu , Takubo Takayuki , Nasu Kaori , Wano Yuji , Sugiyama Taketoshi
Published: February 2007

Two permanent T‐cell leukemia lines designated KH‐1 and KH‐2 were established from the peripheral blood of a 9‐year‐old boy with acute lymphoblastic leukemia and a 47‐year‐old man with adult T‐cell leukemia (ATL). No T‐cell growth factor was used. KH‐1 cells grew as single cells and KH‐2 cells formed clusters in suspension culture. E‐rosette formation, the absence of immunoglobulin determinants and Epstein‐Barr‐virus‐associated nuclear antigen, and the presence of T‐cell antigens revealed by monoclonal antibodies were characteristics of these cell lines as in other established T‐cell leukemia lines. Chromosome analysis at the beginning revealed mosaic presence of cells with 46, XY, t (8q+; 15q‐) and 46, XY which was later completely replaced by the latter karyotype in KH‐1, and abnormal karyotype, 47, XY, +3, t (8q‐; 10p+) was maintained throughout the period of in vitro passage in KH‐2. The donor patient of KH‐2 formerly lived in the south‐western part of Japan where ATL is considered endemic and numerous type‐C virus particles were detected electron microscopically, in KH‐2 cell pellets.
Effect of all‐trans retinoic acid on induction, lethality and immunogenicity of murine methylcholanthrene‐induced fibrosarcomas
Authors: Chauvenet P. H. , Paque Ronald E.
Published: February 2007

The effect of 200 μg doses of all‐trans retinoic acid, given over a long duration (daily for 8 weeks, suspended for 3 weeks, then resumed daily for 4 weeks) or short duration (daily for 30 days), on the induction of fibrosarcomas in C57BL/6J mice by MCA was evaluated. A reduced level of carcinogenesis was observed with both lengths of retinoic acid treatment, since respective incidences of MCA fibrosarcomas were 63 and 61% of those in saline‐treated controls. In other studies, the effect of all‐trans retinoic acid on syngeneic growth of two experimental fibrosarcomas (B6 25 and B6 27, induced previously in C57BL/6J mice by MCA) was assessed. Retinoic‐acid‐treated mice were more resistant to higher doses of viable B6 27 (LD50 = 2.85) and especially B6 25 (LD50 = 3.80) than were corresponding saline‐ or corn‐oil‐treated controls (LD50 <2.0). The strength of resistance conferred by retinoic acid treatment thus varied considerably between these tumors, despite their common strain derivation and histopathological origin. Additional studies explored the effect on B6 27 growth of giving all‐trans retinoic acid during either the sensitization or challenge stage of standard syngeneic immunogenicity tests. Mice given all‐trans retinoic acid during sensitization displayed a markedly increased resistance to challenge with the immunospecific B6 27 tumor (LD50 = 5.30), compared to challenged controls that received saline (LD50 = 2.60) or corn‐oil (LD50 = 2.55) during preimmunization. In contrast, when B6 27‐preimmunized mice were treated with all‐trans retinoic acid after challenge with homologous tumor, resistance to B6 27 (assessed by tumor growth rate and LD50 dose) was not increased but remained comparable to that of salineor corn‐oil‐treated controls. While the mechanism(s) by which all‐trans retinoic acid inhibits syngeneic growth of MCA tumors is unknown, our results support an immunostimulatory effect, evidenced by tumor resistance in both non‐immune and specifically preimmunized syngeneic hosts.
Abrogation of the in vitro generation of the cytotoxic T‐cell response to a murine tumor: The role of suppressor cells
Authors: Frost Philip , Prete Pamela , Kerbel Robert
Published: February 2007

A reproducible in vitro assay for the effect of suppressor T cells on the generation of an in vitro cytotoxic response to a metastatic murine tumor is described. Suppression in this system is maximal. The model uses splenic T cells from DBA/2 mice bearing the MDAY‐D2 metastatic tumor as suppressors of the in vitro generation of a cell mediated cytotoxic response by syngeneic tumor‐bearer (i.e., primed) peripheral lymph node cells stimulated with mitomycin C‐treated MDAY‐D2 tumor cells. The effect of the cell mediated cytotoxic response is profound, specific and mediated by splenic T cells. The suppressor T cells appear to impair precursor rather than mature cytotoxic cells. A highly immunogenic variant of MDAY‐D2, namely MDWI, does not generate a suppressor response. Suppressor T cells from an MDAY‐D2 tumor‐bearer cannot suppress the in vitro response to MDWI. This model of potent suppressor T‐cell action is highly reproducible and offers an opportunity for the analysis of why some tumors generate an effective cell mediated cytotoxic response which others stimulate dramatic suppressor T‐cell response.
Leukemogenic activity of B‐ecotropic C‐type retroviruses isolated from tumors induced by radiation leukemia virus (RADLV‐RS) in C57BL/6 mice
Authors: Legrand E. , Guillemain B. , Daculsi R. , Laigret F.
Published: February 2007

In addition to the endogenous N‐tropic and xenotropic retroviruses in C57BL/6 mice, B‐tropic viruses which result from recombination between the endogenous parental viruses have frequently been isolated from old or leukemic animals. A thymotropic B‐tropic virus was also isolated after many serial in vivo passages from tumors induced by RadLV initially obtained by Kaplan from radiation‐induced thymic lymphosarcomas. Although this agent was shown to be responsible for the capacity of Kaplan RadLV to induce thymic lymphosarcomas (TLS), the oncogenic role of C57BL/6 B‐tropic viruses has never been demonstrated. Three B‐tropic viruses (T1223/B, T128/B and T98/B) were isolated from Duplan (RadLV‐Rs) extract which, like Kaplan isolate, originates from radiation‐induced TLS. Whereas thymotropism was retained by Kaplan extract, extra‐thymic lymphosarcomas were preferentially induced by RadLV‐Rs. Although the B‐tropic isolates emerged from recombinational events between the two endogenous parental viruses, their recombination pattern and their biological in vitro properties indicated that each of them was unique. The present experiments demonstrate, firstly, that in no case was an early disease ressembling that induced by RadLV‐Rs observed; secondly, that the three viruses induced a high percentage of extra‐thymic lymphomas whose latencies always exceeded 400 days; thirdly, that irrespective of the cloned virus a similar pattern of leukemogenesis was observed; fourthly, that B lymphomas predominated over thymic and extra‐thymic T or null lymphoma and erythromyeloid leukemias. The injected viruses shortened the latencies and increased the frequency of the spontaneous disease observed in old animals, which suggests that in both cases leukemogenesis may result from closely related mechanisms. Our observation that the leukemic process developed after a shorter latent period in animals injected at 400 days of age than in those injected at birth or at 30 days of age strongly suggests that the injected viruses need to undergo a second recombination with the endogenous viruses expressed in old mice before they are capable of inducing lymphomas. This hypothesis is supported by the result of the transplantation assay. It does not exclude the possibility of an impairment of the immune responsiveness contributed to the accelerated leukemogenesis in old animals. Thymic and extra‐thymic T lymphomas occurred preferentially in mice injected at birth, indicating that T‐populations present at this age might be necessary for the newly generated T‐tropic recombinants to emerge, replicate or find their target cells.
Cellular ingestion, toxic effects, and lesions observed in human bronchial epithelial tissue and cells cultured with asbestos and glass fibers
Authors: Haugen Aage , Schafer Paul W. , Lechner John F. , Stoner Gary D. , Trump Benjamin F. , Harris Curtis C.
Published: February 2007

Although exposure to asbestos has been shown in previous epidemiological studies to synergistically increase the risk of bronchogenic carcinoma for cigarette smokers, the pathobiological mechanism(s) responsible for the cocarcinogenic action of asbestos is not known. Therefore, the effects of asbestos fibers on normal human tracheobronchial epithelium are of interest. Asbestos fibers, i.e., amosite, crocidolite and chrysotile (UICC samples) and glass fibers were initially assayed for their cytotoxcity. Bronchial epithelial cells exposed to either asbestos or glass fibers displayed inhibition of cell growth as a function of fiber concentration. When compared to glass fibers, asbestos fibers caused a statistically significant (p<0.05) decrease in cell population doubling rate. Chrysotile was approximately 10 times more cytotoxic than either amosite or crocidolite and more than 100 times more cytotoxic than the glass fibers. Epithelial cells were 10 to 15 times more sensitive to the cytotoxic effects of asbestos fibers than bronchial fibroblasts from the same donor. Using electron microscopy, asbestos fibers were seen to be ingested by epithelial cells. After exposure for 2 h short fibers (<12μm) were found both in the cytoplasm and within phagosomes. High‐voltage electron microscopy combined with stereo‐microscopy revealed asbestos fibers in the cytoplasmic matrix. A single exposure to amosite asbestos (100–1000 μg/ml) was found to induce focal hyperplasia and epidermoid metaplasia with cellular atypia in human tracheobronchial explants. Surface fine structure observations revealed asbestos fibers protruding from these lesions. Intra‐cytoplasmic and intranuclear fibers of amosite were identified in these focal lesions using X‐ray microanalysis in combination with transmission electron microscopy. With increasing time, fibers were also seen deposited within the submucosa of the explants. The preferential cytotoxicity of asbestos for epithelial cells and the metaplastic response of bronchial epithelium may be important in the cocarcinogenic action of asbestos.
Lymphoblastic lymphoma: Cytogenetic, pathologic, and immunologic studies
Authors: Kaneko Yasuhiko , Variakojis Daina , Kluskens Larry , Rowley Janet D.
Published: February 2007

Cytogenetic, pathologic, and immunologic studies were done on 10 patients with lymphoblastic lymphoma (LL). The median age was 21 years, and males predominated in a ratio of 9:1. At the time of diagnosis, 6 of the 10 patients had an anterior mediastinal mass, 3 had bone marrow involvement, and 2 had central nervous system involvement. All patients were treated with intensive combination chemotherapy. The median survival of the 8 patients who died (7 of whom were adults) was 10.5 months; all 8 achieved only a partial remission. Two other patients were children; they continue in complete remission. Immunologic marker studies were done on 9 of the patients; 5 had T‐cell LL, and the other 4 had non‐T, non‐B LL. In a study of T‐cell subpopulations with the use of monoclonal antibodies, the malignant T cells of the 2 patients tested appeared to be mature thymocytes. Clonal chromosome abnormalities were seen in involved tissues from 8 patients; the other 2 patients had a normal karyotype. A 9q+ chromosome, a 6q‐chromosome, and a 1q‐chromosome associated with 1q trisomy were each seen in 2 patients. No patient had a 14q+ chromosome, which is the most common abnormality in various lymphoproliferative disorders, including other T‐cell malignant diseases. The variable chromosome pattern in LL could be related to the heterogeneity of the immunologic phenotype of the malignant T cells. More data are needed before it can be established whether there are any correlations between a particular karyotype and the immunologic phenotype of LL cells.
Isolation and characterization of retrovirus‐like elements from normal human fetuses
Authors: Mondal Hrishikes , Hofschneider Peter Hans
Published: February 2007

Retrovirus‐like particles have been isolated from normal fetal human plasma and from different embryonic organs collected from late first‐trimester fetuses. The majority of the virus‐like particles banded at a density region of 1.19–1.22 g/ml, although lighter particles having a density of 1.15–1.17 g/ml were observed in some fetal tissues. The particles appeared similar to retroviruses when viewed electron‐microscopically. They contained reverse transcriptase (RT) which accepted oligo (dG)‐poly(C) in Mn+2 over other synthetic template‐primers and transcribed heteropolymeric RNAs primed with oligo (dT). The enzyme was partially (40%) inhibited by the antiserum against RT of feline endogenous virus (RD114) and not at all by the antisera against RT of avian myeloblastosis virus (AMV), spleen necrosis virus (SNV) and gibbon ape leukemia virus (GALV). The simultaneous detection test in the presence of actinomycin D revealed that the particles contained high mol. wt. (70 S and 35 S) RNAs. The single‐stranded DNA complementary to RNA of the human fetal particle hybridized to DNA obtained from different tissues of human adults, showing that the nucleic acids of the virus‐like particles were endogenous. The particles could be isolated only from the embryonic organs during differentiation. This suggests that the retroviral gene expression is correlated with embryonic differentiation. These particles could not be induced and as yet infectivity has not been demonstrated, therefore, they are at present described as retroviral elements, not as retroviruses.
Armed human monocytes challenged with a sensitizing cancer extract release substances pharmacologically similar to leukotrienes
Authors: Thomson D. M. P. , Phelan Kerry , Morton Douglas G. , Bach Michael K.
Published: February 2007

Human peripheral blood monocytes were highly enriched by adherence to plastic, armed with serum from cancer patients, and challenged separately and simultaneously with the sensitizing and unrelated cancer extracts. The response of the monocytes was to release a factor that inhibited leukocyte adherence (LAI)4 to glass. The macrophage‐like cell line U937 released a similar factor when it was armed and challenged with the sensitizing cancer extract. The production of the factor was blocked by 10−6 M ETYA and 10−6 M NDGA but not by 10−6 M indomethacin. Moreover, a competitive inhibitor of leukotriene function, 10−6 M FPL55712, blocked the LAI reaction mediated by the factor. Arylsulfatase destroyed its activity while depletion of the monocytes' cellular glutathione pool with CyH or Et2Mal stopped production of the mediator. Pure leukotrienes (C and D) in a dose‐response fashion prevented the adherence of leukocytes to glass; the nonadherence of mononuclear cells was equal to that of polymorphonuclear cells. PGE2, if added to the leukocytes immediately before challenge with LTC or LTD, increased 1,000‐fold the leukocytes' sensitivity to the leukotrienes. Paradoxically, if leukocytes were washed and exposed to PGE2 15 min after being challenged with leukotrienes, their normal glass‐adherence property and the ability to respond again to LTD were restored. FPL 55712 blocked the effect of LTC and LTD from inhibiting the adherence of leukocytes to glass. The present study shows that human monocytes armed with cytophik antitumor antibody, when challenged with the sensitizing cancer extract, release leukotriene(s) as shown by pharmacologic evidence, implying that monocytes may play an important inflammatory role in human cancer.
Effect of retinoic acid on the spontaneous and interferon‐induced activity of human natural killer cells
Authors: Abb Jochen , Abb Hannelore , Deinhardt Friedrich
Published: February 2007

Non‐toxic concentrations of retinoic acid (RA) inhibited the spontaneous activity of human natural killer (NK) cells. RA also inhibited the activation of human NK cells by treatment with partially purified human leukocyte interferon (HulFNα) or with inducers of IFNα and IFNγ. Full expression of the inhibitory action required prolonged exposure of human peripheral blood leukocytes to RA. Implications of these findings for the use of retinoids in the treatment of human malignancies are discussed.
Modulation of antigen‐induced leukocyte adherence inhibition by metabolites of arachidonic acid and intracellular nucleotides
Authors: Thomson D. M. P. , Phelan Kerry , Scanzano Rosemarie , Fink Aaron
Published: February 2007

After binding a sensitizing tumor antigen, human leukocytes undergo a series of changes that lead to a loss of their glass‐adherent properties; a phenomenon called leukocyte adherence inhibition (LAI)1. After surgery or when patients have a large tumor burden, their test results become negative. This study shows that in vitro incubation of the leukocytes for 5 min with PGE2 converted to positive the negative test, in an immunologically specific manner. The effect was critically dose‐dependent, too little or too much did not alter the result. The same effect was achieved with PGE2, PGI2, aminophylline or other drugs that raise intracellular nucleotides, including dibutyryl cyclic AMP and dibutyryl cyclic GMP. Dibutyryl cyclic AMP stimulated a stronger response and 100 times less was needed than of dibutyryl cyclic GMP. Prostaglandins did not mediate LAI since Indomethacin failed to inhibit a positive test. Nonetheless, arachidonate metabolites were critical for the LAI phenomenon since BPB and mepacrine, inhibitors of phospholipase A2, negated the LAI response. Moreover, ETYA, phenidone and NDGA, inhibitors of the lipoxygenase metabolic pathway, all negated the positive LAI response. The positive response was especially sensitive to nullification by ETYA. Although the last‐named drugs inhibit other arachidonate metabolic pathways too, conclusive evidence that the matabolites of the lipoxygenase pathway, and leukotrienes in particular, mediate the LAI response was the fact that FPL 55712, a competitive antagonist of SRS, nullified a positive response at levels as low as 10−13 M. The results imply that prostaglandins were able to modulate the expression of LAI by affecting intracellular nucleotides, but leukotrienes, it seems, were the metabolites that mediated leukocyte nonadherence after monocytes recognized and bound tumor antigen.
Procoagulant and fibrinolytic activities of gastric and colorectal cancer
Authors: Szczepańaski Maciej , Lucer Cezary , Zawadzki Jakub , Tołłoczko Tadeusz
Published: February 2007

Procoagulant activity (PA) and fibrinolytic activity (FA) were investigated in 14 specimens of gastric cancer (GC) and in 26 specimens of colorectal cancer (CC) and simultaneously, in samples of the normal mucosa obtained from the same organs. Histochemical localization of plasminogen activator was performed at the tumor borderline. The PA of the tumor extracts was in most cases lower than in the corresponding normal mucosa from GC as well as CC patients. The FA of the extracts of CC was also lower than that of normal mucosa. On the other hand, 11 of 14 cases with GC showed a significantly higher FA in the tumor extracts than that in the corresponding normal mucosa. The histochemical localization of plasminogen activator revealed that its activity is connected with small and medium‐sized blood vessels, but not with the cells of the two kinds of cancer investigated. Morphological and histochemical findings from both kinds of cancer demonstrate that the FA of their extracts depends on the vascularity of specimens of the respective tumors.
Correlation between the metastasizing activity of in vitro spontaneously transformed hamster cells and their natural resistance‐depressing activity
Authors: Deichman G. I. , Kluchareva T. E. , Kashkina L. M. , Matveeva V. A. , Vendrov E. L. , Zemtsova V. I.
Published: February 2007

In our previous experiments in Syrian hamsters the in vivo semiquantitative method of determination of the natural resistance‐depressing (NRD) activity of tumor cells was described. It was demonstrated that inactivated cells of different tissue culture cell lines derived from in vivo tumors in contrast to normal, or in vitro spontaneously transformed hamster embryo (STHE) cells, bear the NRD factor. It was suggested that NRD activity of tumor cells might be essential for the development of primary tumors and metastases (Deichman et al., 1979). Therefore, in this study we compared the NRD activity and metastatic activity (MA) of the parelal STHE cells never passaged in vivo and STHE in vivo sublines, obtained from subcutaneous tumor nodules and from individual spontaneous lung metastases (LM) after s.c. transplantation of STHE cells. Five LM sublines of STHE strain (out of eight investigated) were NRD active as well as the cells of one of two s.c. tumor nodules. Study of MA, i.e. the relation between the number of cells inoculated retroorbitally in the bloodstream of hamsters and the number of experimental metastases developed in the lungs of inoculated animals, demonstrated that the highest MA was observed with the cells of LM sublines possessing the highest NRD activity. Parental STHE cells did not depress natural anti‐tumor resistance and their MA was the lowest. The data presented demonstrate the heterogeneity of the population of constantly cultured in vitro STHE cells in relation to their NRD activity and the selection of NRD active cells during the development of lung metastases.
Papillary carcinomas of the thyroid have pore‐deficient nuclei
Authors: Johannessen Jan Vincents , Sobrinho‐Simöes Manuel , Finseth Inga , Pilström Lars
Published: February 2007

A significant reduction in nuclear pore density observed in papillary carcinomas compared to normal thyroid, adenomas and follicular carcinomas probably disturbs the nucleo‐cytoplasmic transfer of ribonucleoproteins. This may contribute to the slow growth and indolent biological behavior of these tumors where even the presence of regional lymph node metastases does not worsen the prognosis. The signs of nuclear hyperactivity may result from an attempt to compensate for the nuclear membrane defect.