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In vitro adsorption of colon cancer sera over staphylococcus protein A: lymphocyte stimulation by leakage of adsorbance.

Serum factors may be responsible for reduced host-anti-tumor defence. Although there is still confusion about their origin, attempts have been made to immobilize serum components by Protein A columns as a therapeutic modality. In our study the in vitro adsorption of 90% of the IgG from cancer sera on "immobilized protein A" did not influence the inhibitory serum activity as measured in a mixed lymphocyte culture. Therefore, IgG or immune complexes do not seem to be the suppressive serum factor in patients with advanced colorectal carcinoma. There is evidence for leakage of small amounts of protein A from the columns which have immunostimulatory activity. Perhaps this may explain necrosis after a therapeutic immunoadsorption.

Adsorption↗

Benign mixed epithelial stromal tumor of the renal pelvis with exophytic growth: case report.

BACKGROUND: Mixed epithelial and stromal tumor (MEST) is a distinctive benign composite neoplasm of the kidney predominantly seen in females mostly in the perimenopausal period. Although these tumors are known to arise from renal pelvis, our case was distinct in that it had no intrapelvic component growing in exophytic fashion. CASE REPORT: A 35 year old female patient presented to us with vague abdominal pain. She had undergone excision of bilateral ovarian cystic masses for cystic teratoma twelve years earlier. A computed tomography scan of abdomen and pelvis showed a 9 x 7 cm uniformly solid mass with poor contrast enhancement situated in the inferomedial aspect of the left kidney. On exploration, the mass was arising from the inferior and anterior aspect of left renal pelvis, and was attached to it with a narrow pedicle. There was no adherence or attachment to the renal parenchyma. The mass was excised preserving the kidney. Microscopically, the tumor was composed of large collagenized areas containing bundles of spindle cells and several 'microcysts' lined by cuboidal epithelium suggestive of a benign mixed epithelial stromal tumor. DISCUSSION: Mixed epithelial tumors usually present in perimenopausal women as a partially cystic mass. Tumors are composed of irregular mixtures of cystic and solid areas, glands with variable complexity and distribution and the stromal component is characterized by a spindle cell proliferation. Commonly, it arises from the renal parenchyma and pelvis and nephrectomy is advocated to manage these tumors. CONCLUSION: MEST is a distinctive benign tumor of the kidney that should be distinguished from other renal neoplasms. MEST arising from the renal pelvis and growing exophytically is a rare entity. The overall prognosis is favorable.

Journal Article↗

Pesticides and cancer risks in agriculture.

The work environment in agriculture is complex, with many potentially hazardous exposures, but the overall mortality from cancer and other causes is rather low among farmers. However, several studies have consistently indicated an excess of certain cancer forms. Lymphomas, leukemias, multiple myeloma and also malignancies of connective tissue attract special interest, as being possibly associated with the use of pesticides. Phenoxy acid herbicides may play an etiological role, especially for non-Hodgkin's lymphoma, whereas the findings are more ambiguous for Hodgkin's disease and soft-tissue sarcoma, perhaps indicating an interaction with co-factors. The issue has been controversial for many years, however, and one of its aspects involves the use of phenoxy acids in the Vietnam war. Furthermore, DDT has been associated with lung cancer in mixed exposure situations, and with chronic lymphatic leukemia. Arsenical pesticides may have caused skin cancer in vine-growers. Further studies, especially of specific user groups and producers, may avoid the complex exposure situation in agriculture.

Agricultural Workers' Diseases↗

Studies of cloned Friend erythroleukemia tumor cells. Modulation of the tumor-specific cytologic T lymphocyte response by infectious Friend virus production in vitro.

The HFL/b tumor cell line, induced by Friend erythroleukemia virus in BALB.B mice, was used to study the relation between virus production or nonproduction and the antigens recognized by Friend virus-specific cytolytic T lymphocytes (CTL). Analysis of clones and subclones of these tumor cells revealed a high degree of heterogeneity with respect to the production and release into culture fluids of infectious Friend virus in vitro, ranging from high levels to low or undetectable levels of virus production. Although no major differences could be detected among the antibody-defined serotypes of the various clones, the susceptibility of cells of individual HFL/b clones to attack by Friend virus-specific CTL varied widely, and those clones which produced large amounts of infectious virus provided the most sensitive target cells. It was also apparent that production of infectious Friend virus was inhibitory to CTL generation in syngeneic mixed leukocyte-tumor cell cultures. Friend erythroleukemia virus-producing cells thus appeared to interact in a complex manner with the host CTL response by modulating their production of infectious Friend virus.

Animals↗

Tumour-induced suppression of immune response and its correction.

Immunosuppressive features of tumour cells are a major obstacle for immunotherapy of cancer. We recently noted that RENCA cells effectively interfere with the in vivo activation of RENCA-specific T cells. To unravel the underlying mechanism, we evaluated the influence of RENCA cells on a mixed-lymphocyte/ tumour reaction as well as an allogeneic mixed-lymphocyte reaction. We observed that RENCA cells were not directly immunosuppressive. Instead, they initiated deviation of an immune response in at least two independent directions: (i) expansion of a population of NK1.1+/CD3+ cells, which was accompanied by elimination of mainly CD4+ lymphocytes, and (ii) production of a leukocyte-derived inhibitory factor. Expression of the costimulatory molecule B7.1 by RENCA cells prevented induction of anergy, while expression of MHC class II molecules prevented expansion of NK1.1+ cells, which was accompanied by a significant decrease in cell death. Hence, an unimpaired response was observed only when RENCA cells expressed B7.1 plus MHC class II molecules. Thus, even if a tumour itself is not immunosuppressive, it can induce a strong deviation of the immune response. It is concluded that the first contact between elements of the immune system and the tumour cell can confer a severe bias on immunoregulatory circuits.

Animals↗

Suppression of polyclonal, tumor cell and alloantigen-induced proliferation: identification of cyclooxygenase pathway dependent and independent mechanisms.

Polyclonal T cell activation, syngeneic tumor cell and alloantigen-induced proliferative responses were studied to determine if the regulation of these responses in normal and tumor-bearing NBR rats is mediated through products of the cyclooxygenase pathway and prostaglandin E2 (PGE2) in particular. Young rats and tumor-bearing rats have previously been shown to produce poor proliferative responses to PHA, Con A and syngeneic methylcholanthrene (MCA)-induced fibrosarcoma cells. The poor responses to PHA and Con A are mediated by PGE2 in unfractionated ( UNF ) and nylon wool adherent (ADH) cells. The same relationship was also established in the mixed leukocyte tumor cell (MLTC) response to MCA tumor cells although it appears to be of only minor significance as the enhancement following indomethacin (IND) treatment is still a relatively poor response. Indomethacin generally had no effect on the proliferative responses of tumor-bearing animals indicating that the suppression was not mediated through the cyclooxygenase pathway. We have also extended a previous observation in which UNF cells were found to be unresponsive to alloantigen stimulation. This suppression does not appear to be mediated through cyclooxygenase products as IND treatment does not enhance the UNF response although it does enhance the ADH response. These data indicate that a complex network of cyclooxygenase dependent and independent regulation exists in normal and tumor-bearing NBR rats.

Animals↗

Immunocompetence in lung cancer patients: analysis of serological and cellular parameters.

Some serological (serum immunoglobulins, circulating immune complexes, quantitative assessment of hemolytic complement activity) and cellular (total number of circulating lymphocytes as well their phenotypic and functional characterization) parameters have been analyzed in 42 patients with lung cancer of three hystologic types and in 19 healthy controls to define whether different histologic neoplasms have an impact on the host immune system. As a group, cancer patients showed 1) the presence of circulating immune complexes, in a significant percentage, within all the three groups studied; and 2) a significant reduction of lymphocytes forming E rosette. With regard to cellular immune parameters we noted that 1) T lymphocytes isolated from the peripheral blood lymphocytes (PBL) of patients with lung cancer showed a decreased capacity to express HLA-class II antigens upon phytohemogglutinin (PHA) activation in vitro; 2) PBL from lung cancer, in particular the adenocarcinoma group, failed to proliferate upon stimulation by policlonal mitogens; and 3) the autologous mixed lymphocyte reaction (MLR) of non-T/T-type was impaired in all three groups, whereas the autologous MLR of T/T-type was impaired only in the patients with squamous cell carcinoma and in those with adenocarcinoma, probably as a result of a reduced stimulatory capacity.

Adenocarcinoma↗

RNA tumor virus genes and the transforming genes: genetic transmission, infectious spread, and modes of expression.

The genetic conservation and evolution of virogenes in mammalian species are described in relation to the horizontal, vertical, and congenital transmission of type C RNA oncogenic viruses within members of a given species, or among members of near and/or distantly related species. Examples of oncogenic virus infection between ancestors of the mouse, cat, pig, and primates as well as the integration of the virus into the host's genome are documented. The possible normal functions of the virogenes as a part of the cellular genome of many species are explored. Recent evidence of genetic recombination (genetic mixing) among distinct type C viruses is also reviewed, thus completing an overview of the evolutionary past, present, and complex future relationships of oncogenic RNA viruses and mammalian species.

Animals↗

The presence of tumour-specific membrane antigen in the serum of rats with chemically induced sarcomata.

Antibodies to the tumour-specific transplantation type antigen (TSTA) of a transplanted methylcholanthrene-induced sarcoma (MC-1) in syngeneic rats were studied using the techniques of indirect membrane immunofluorescence and mixed haemadsorption with a (51)Cr-labelled indicator cell. After tumour excision, anti-TSTA antibody was readily measurable in both serum and lymph. In contrast, the tumour-bearing animal had no measurable anti-TSTA antibody in the serum but low titres in the lymph. Consequently, we formed the hypothesis that in the presence of a growing tumour the serum contained antigen-antibody complexes with antigen in excess.To test this hypothesis, tumour-bearing serum was examined for the presence of free antigen and antigen-antibody complexes by 2 different methods. In the first method, tumour-bearing serum was cross-linked with glutaraldehyde and was found to absorb specifically the anti-TSTA antibody, indicating free circulating TSTA. Next, antigen-antibody complexes were split with salt or acid and separated into a low molecular weight (or "antigen") fraction (<100,000) and a high molecular weight (or "antibody") fraction (>100,000). The low M.W. fraction specifically inhibited the anti-TSTA antibody when tested by either membrane immunofluorescence or mixed haemadsorption, indicating the presence of antigen from antigen-antibody complexes in the tumour-bearing circulation. The possible effect on the host's immune response of circulating free tumour antigen and antigen-antibody complexes are discussed.

Animals↗

Comparison of lymphocyte reactivity in patients with cancer, systemic lupus erythematosus and renal allografts.

The PHA and MLC reactivity of lymphocytes from patients with cancer, SLE or renal allografts was comparatively tested in the presence of autologous and of normal homologous serum. Sera from patients with advanced cancer, active SLE or chronic allograft rejection strongly inhibited the MLC reactivity of autologous lymphocytes. It is suggested that serum inhibitory factors might be antibodies which are directed against modified antigenic determinants of the major histocompatibility complex, and are capable of blocking T lymphocyte receptors.

Humans↗

Molecular analysis of 13 cases of MLL/11q23 secondary acute leukemia and identification of topoisomerase II consensus-binding sequences near the chromosomal breakpoint of a secondary leukemia with the t(4;11).

Rearrangements of the MLL (Mixed Lineage Leukemia) gene in the human 11q23 cytogenetic locus have been detected in secondary (therapy-related) acute leukemias in patients who have received topoisomerase II inhibitors for prior, independent neoplasms. The topoisomerase II inhibitors implicated in MLL/11q23 secondary leukemias all inhibit the religation step of reaction catalyzed by topoisomerase II. This results in the stabilization of a 'cleavable complex' with double-strand DNA breaks at the point of topoisomerase II binding. This raises the possibility that the cleavable complex participates in the translocation process in MLL/11q23 secondary leukemias. Here we report that the MLL/11q23 breakpoints in 13/13 patients with secondary leukemia map to the same breakpoint cluster region (bcr) noted in de novo MLL/11q23 acute leukemias and the presence of in vivo topoisomerase II inhibitor-induced cleavage sites in MLL/11q23 bcr. We have also cloned and sequenced the breakpoint from a MLL/11q23 secondary acute leukemia. This analysis revealed sequences similar to the consensus sequence for vertebrate topoisomerase II binding and cleavage close to the 11q23 and 4q21 breakpoints. These results support a role for topoisomerase II in mechanism generating translocations in MLL/11q23 secondary acute leukemia.

Acute Disease↗

Mixed odontogenic tumours and odontomas. Considerations on interrelationship. Review of the literature and presentation of 134 new cases of odontomas.

Based on a world-wide literature survey of published cases of "mixed odontogenic tumours" (ameloblastic fibroma, fibrodentinoma and fibro-odontoma) and complex/compound odontomas (including 134 own cases of odontomas) the authors present data showing the complex nature of these lesions. The authors suggest the following work hypothesis regarding the pathogenesis and relationship between the "mixed odontogenic tumours" and the odontomas. The tumours develop along two separate lines: (I) the neoplastic line comprising only one tumour, the ameloblastic fibroma (AF) and the closely related ameloblastic fibrodentinoma (AFD). (II) The hamartomatous (or the developing complex odontoma (DCO) line comprising: (1) The AF (and AFD). Differences in age and biological behaviour indicate that some AF are true benign neoplasms, whereas others are hamartomas presenting the first stage in the DCO-line. (2) The AF-O represents the second stage of the DCO-line developing into (3) the fully mineralized complex odontoma. Lastly, the authors suggest that the compound odontoma should be considered not as an alternative final stage to the complex odontoma but rather as a malformation (with a high degree of histomorphological differentiation) pathogenetically closely related to the process producing hyperodontia, "multiple schizodontia" or locally conditioned hyperactivity of the dental lamina.

Adolescent↗

Isolation and characterization of proteoglycans synthesized by human colon and colon carcinoma.

The biosynthesis of proteoglycans in short term organ culture of human colon and colon carcinoma was studied. Proteoglycans, labeled with [35S]sulfate and [3H]serine, were extracted with either 4 M or 0.5 M guanidine HCl in the presence of protease inhibitors and sequentially purified by associative and dissociative CsCl density gradient ultracentrifugation. Normal colon synthesized two polydisperse classes of proteoglycans: a large heparan sulfate-containing monomer, with a Kav of 0.48 on Sepharose CL-2B and a small dermatan sulfate-containing monomer with a Kav of 0.65. A portion (25%) of the proteoglycans was found as aggregate when chromatographed under associative conditions, and the larger monomers interacted with hyaluronic acid to an extent greater than the smaller proteoglycans. Following papain or alkali treatment, the free glycosaminoglycan side chains of both monomers eluted as a single broad peak (Kav = 0.5) from Sepharose CL-6B, with an estimated Mr of 20 X 10(3). In contrast, colon carcinoma synthesized only one proteoglycan monomer, which aggregated to a limited extent (12%). This proteoglycan population, with a Kav of 0.7 on CL-2B, contained chondroitin sulfate as the major glycosaminoglycan (greater than 81%), with small amounts of dermatan sulfate. The glycosaminoglycans had an estimated Mr of 9 X 10(3), and the disaccharides released by chondroitinase ABC consisted of 32% 4-sulfate and 68% 6-sulfate. Electron microscopy of mixed proteoglycancytochrome c monolayers from the associative fractions of normal and neoplastic colon revealed aggregated complexes which were similar in over structure, although smaller than the proteoglycan aggregates from cartilage.

Amino Acids↗

Cytologic differentiation of benign from malignant canine mammary tumors.

Cytologic and histologic examination of 91 canine mammary masses was performed by two cytologists and two histopathologists. Ten important cytologic criteria of malignancy for canine mammary tumors were identified. A cytologic grading system for differentiation of benign from malignant mammary tumors was proposed using these criteria. With this system, approximately one fourth of the malignant mammary tumors were given a concordant cytologic diagnosis. Approximately one-half of the benign masses were given a concordant cytologic diagnosis by the two cytologists. One-half of all the tumors examined were given inconclusive cytologic diagnoses by both cytologists. The cytologic identification of spindle cells did not differentiate complex and mixed mammary tumors from simple tumors. Only five of the animals studied died of mammary cancer, precluding a critical analysis of the cytologic criteria for prediction of cancer mortality.

Animals↗

Sinonasal teratocarcinosarcoma: an unusual neoplasm.

Sinonasal teratocarcinosarcoma (SNTCS) is a very unusual and aggressive neoplasm characterized by the combination of malignant teratoma and carcinosarcoma features, of which less than forty cases have been reported in the literature. We report on a 75-year-old man with SNTCS that involved the left ethmoid, maxillary and sphenoidal sinuses. The tumor showed a complex histological pattern with mature and immature glands, benign squamous and malignant poorly differentiated epithelia, as well as neuroblastoma-like tissue and sarcoma component with rhabdomyoblastic differentiation. This peculiar blend of tissue types makes the diagnosis of this entity a difficult challenge, especially in small biopsies or in tumors only partially removed. This tumor must be differentiated from several types of carcinomas, esthesioneuroblastoma, craniopharyngioma, malignant mixed tumor of salivary gland type and germ cell tumors. The present case represents, to our knowledge, the third SNTCS described in the european literature.

Aged↗