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Biomedical subjects

H E Kaiser

Publications and source records attributed to H E Kaiser.

At least 109 records · Page 6Linked to original sources
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Hodgkin's disease: treatment and secondary neoplasms.

Hodgkin's disease is a lymphoma which occurs in man in the lymph nodes or in extra-lymphatic tissue. The disease was first described in 1832 by Thomas Hodgkin, a British physician. The disease develops with different patterns of histology in several types which a varying degree of malignancy: stages of the disease processes may be encountered. Lymph nodes appear phylogenetically first in the mesentery of crocodiles and reach the top of their development in the mammal. Here they are important during the neoplastic development as regional stations thereof. The treatment, depending on the cellular make-up of the type, may vary from advantageous to very toxic. Successful treatment in several cases on the one hand, in contrast to high therapeutic toxicity, and the development of secondary neoplasms on the other, are outlined.

Adult↗
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Synergistic cytotoxic and antitumor effects of irradiation and taxol on human HeLa cervix carcinoma and mouse B16 melanoma cells.

Several articles have appeared in the scientific literature which report that taxol has the ability to block and/or prolong cells in the G2/Mp phase of the cell cycle by inducing extremely stable microtubules. The G2/M phase is known to be the most radiosensitive phase of the cell cycle. It is the purpose of this study to evaluate the effect of combination taxol and ionizing radiation on tumor cell lines which have not been previously reported in the literature. Decrease in viability and inhibition of proliferation of HeLa and B16 cells induced by irradiation were dose-dependent and significantly enhanced by pretreatment the cells with taxol. Similar antitumor effects of irradiation and taxol were demonstrated by flow cytometric analysis of chromatic fragment formation induced in these cells. The exact mechanism by which taxol enhanced the tumoricidal effect of irradiation is not known. Cell cycle analysis showed that taxol was effective in blocking HeLa and B16 cells at the G2/M stage, at which the tumor cells are believed to be most sensitive to irradiation. This study is in agreement with others who have found that taxol is a powerful radiation sensitizer. Clinical research protocols have been developed and are under way to determine if taxol produces similar synergistic effects in patients undergoing radiation therapy.

Animals↗
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Interspecies comparative pathology of colorectal neoplasms: relevance for treatment.

Comparative pathology may serve as a practical tool for therapy by comparison of normal and abnormal structures of the digestive tract in animals and men. A better understanding of colon cancer as the most common solid neoplasm after lung cancer in the industrialized world is sought. In the so-called developed nations and in animals colon cancer is less frequent. The pathogenesis of colon cancer involves environmental and genetic factors. Several types of colorectal cancer can be discerned and the species distribution ranges from invertebrates to man. Colorectal neoplastic progression is species-specific. An intraspecies-specific comparison of large bowel cancer is also valuable. Alteration of signal transduction pathways and somatic mutations of oncogenes are described, as well as the occurrence, research and current treatment. Metastasis of neoplasms of the colon and of the rectum can be studied by intraspecies-specific comparison. Sections of this review deal with vitamin D and cancer and close with present therapies for colorectal cancer.

Animals↗
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Biological viewpoints of neoplastic regression.

Progression during the growth processes, normal and pathologic, serves the production of new structures. On the contrary, regression serves the destruction of structures in the normal and pathologic organism. In the case of catastrophic development (as in homometabolic insects), the regressive processes, known there as autolysis or histolysis respectively, open the way for structural replacement followed by replacement of the removed structures by new ones. This process may be called normal indirect regression, whereas the regression of malignant neoplasms is better termed direct regression because it is not followed by a replacement. Oncologic interest is concerned mainly with the development of neoplastic growth, whereas the spontaneous regression has been rather neglected, even though its understanding may offer therapeutic possibilities in human and veterinary medicine. This paper offers some new thoughts based on recent cases of neoplastic regression.

Animals↗
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Abnormal growth processes in plants and animals: a comparison.

Tumorigenesis in eukaryotic organisms is based on the deregulation of normal cell growth and development. This deregulation may be elicited by external as well as endogenous factors. We distinguish between benign and malignant growths depending on the inducing tumorigenic agents and on the genetic make-up of the affected organism. This review discusses similarities of neoplasmatic (epigenetic) and neoplastic transformations in plants and animals as well as inherent differences in the growth parameters between the two kingdoms. Examples given for neoplasmatic tissues are the hyperplasias and insect galls (zoocecidia) in plants and hypoplasia, aplasia and agenesis in animals (and man). Neoplastic transformation in plants is the result of either the incorporation of foreign nuclear material into the plant genome or an imbalance of inherited chromosomes (in hybrids). Examples for neoplasias are the crown gall disease and Kostoff's genetic tumors in plants, and the carcinomas and leukemias in animals. The more than 80 year old, but neglected, concept of a correlation between tumorigenesis in animals and plants has been revived through advances in molecular and cell biology and molecular genetics which will stimulate a new form of biological reasoning and thought, fueled by new insights into cellular regulatory processes.

Animals↗
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Recombinant human interleukin-1 alpha: a potent bio-immunomodifier in vivo in immunosuppressed mice induced by cyclophosphamide, retroviral infection and surgical stress.

Recombinant human Interleukin-1 Alpha (rhu IL-1 alpha) was assessed for its efficacy in modifying the immunosuppression of mice compromised by Cyclophosphamide (CY), retrovirus infection or surgical stress. Sublethal dose (300 mg/kg) of CY caused neutropenia, decreased cellularity of bone marrow and inhibited Natural Killer (NK) cell activity and lymphokine-activated killer (LAK) cell activity in DBA/2 mice. A single dose of rhu IL-1 alpha (1000 units/per mouse) i.p. accelerated recovery of blood neutrophils and bone marrow cellularity and restored NK and LAK cell activity in CY-treated mice. Mice infected with Friend Virus Complex (FVC) had decreased percentages of L3T4+ cells and a reversed L3T4+/Lyt-2+ ratio; NK and LAK cell activity also decreased. These impaired cellular parameters were restored by rhu IL-1 alpha treatment (1000 units/per mouse/daily i.p. starting on day 5 for 5 days). NK and LAK cell activity was impaired by surgical stress. A single dose of rhu IL-1 alpha (1000 units/per mouse) i.p. 20 hours before transfemoral amputation restored NK and LAK cell activity to normal levels in these mice. These studies indicate that rhu IL-1 alpha possesses immunomodulatory effects in vivo for a broad range of stresses.

Animals↗
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Comparison of direct spreading and local recurrence of neoplasms.

Neoplastic progression proceeds most commonly with metastatic spreading but also with direct spreading and some minor forms of neoplastic distribution. The difference between metastatic spreading and direct tumor spreading is shown by the fact that metastatic cells are motile and separate from the primary tumor, whereas in direct spreading the progressing cells are less motile and connected with the primary tumor. This latter type of spreading is especially common in kidney cancers. In the case of local recurrence where portions of the primary tumor have been spared from destruction, regrowth of these portions may occur after different intervals. It is a precondition that the neoplastic metabolism has gained power again. Local recurrence is an offspring of growth from the primary tumor or from a not fully removed metastasis and should be considered as a growth comparable to direct spreading. It may switch during further progression to metastatic progression.

Female↗
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Therapeutic possibilities and opportunities for comparative oncopathology.

In reviewing abnormal growth, we may distinguish autonomous and nonautonomous growth processes. The highest diversification is reached in the autonomous non-self-limiting processes, the malignant neoplasms which, if not treated, are characterized by extensive growth and progression. In their development these processes exhibit autonomy on one hand and heterogeneity on the other. Neoplastic and related diseases are extremely complex. It is unacceptable to view them exclusively as genetic or metabolic diseases, or merely as the tumor itself, including its progressive stages, as evidenced in neoplastic metastasis. All these characteristics appear in the different types of neoplastic malignomas, e.g. genetic variations in the neoplastic cells from the normal cells of the parent tissue(s). Included here are tumor progression and cloning of the neoplastic cells, stagewise development of host metabolism and of tumor metabolism; neoplastic hereditary and endocrine-like syndromes as well as paraneoplastic syndromes and cachexia. Neoplastic progression, as observed in the metastatic cascade, derives from the cells of the primary tumor. In contrast, multiple primary tumors originate from different host tissues, whereas the syndromes themselves constitute a symptom complex developing in a neoplasm-bearing host and cannot be assigned to local or distant spread of neoplasms. The only possible explanation for these apparently contrasting processes lies in the interaction of tumor and host metabolism, which seemingly varies in tumor-bearing hosts and in those cases where the tumor has been surgical removed. Antigens and other compounds again show an increase with the usually ensuing secondary tumor spread, a course which provides the basis for most deaths from cancer.

Aging↗
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The role of dendritic cells in the motility of melanoma cells in initial lymphatic metastasis.

Malignant melanoma is well known for its aggressive metastatic behavior, following upon the earliest initial stages. It is the purpose of this preliminary paper to add some new ideas, based on electron microscopy, to our understanding of the complex progression of malignant melanoma, using cutaneous melanoma as a model for the subtypes. Special attention is paid to cellular interaction in the progression of melanoma, with emphasis on the subtypes.

Cell Movement↗
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Electron microscopic investigations of progressive early metastasis of cutaneous melanoma.

Primary metastasis of cutaneous malignant melanoma seems to occur especially via the initial lymphatics (IL). In samples of 50 melanomas examined by TEM melanoma cells (MCs), invading IL were demonstrated in 24 specimens. MCs were scarcely found in the immediate vicinity of blood vessels. After the MC has escaped from the MC-complex, connective tissue fibers and cells represent physiological guide-ways that lead the MC to the IL. Located close to the IL, the MC develops pseudopodium-like cytoplasmic processes that penetrate the abluminal fibrous network, fuse partially with the endothelium and destroy it. It seems to be important that the melanomas invade IL as single cells and not in form of cell clusters.

Humans↗
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Soluble interleukin-2 receptors in sera of children with primary malignant neoplasms.

PURPOSE: T lymphocyte activation regulates the autocrine type secretion of interleukin-2, a T cell growth factor and the de novo expression of its cell-surface receptor (IL-2R). Afterwards, a special, truncated form of the IL-2R is secreted into the serum as a soluble molecule. Soluble interleukin-2 receptor (sIL-2R) in serum is non-specific marker of common activation of the cellular immune regulation. This study reports the results of an early diagnostic observation of sIL-2R level in the sera of 18 primary solid pediatric malignancies. PATIENTS AND METHODS: 18 children between the ages of 1 and 12 represented the Study Group of solid tumor bearing patients. 12 healthy children between the ages of 1 and 12 represented the Control Group. Concentrations of sIL-2R were detected in the sera of the children employing a double-antibody sandwich enzyme-linked immunosorbent assay (T Cell Sciences). RESULTS: Control Group concentrations of sIL-2R were in the range of 101.9 to 255.3 IU/mL with a mean value of 178.6 IU/mL. Serum levels of sIL-2R were markedly elevated in the sera of children with solid tumors (Study Group) to levels between 223.8 IU/mL and 927 IU/mL with a mean value of 575.4 IU/mL. CONCLUSIONS: 1) The shedding of cell-surface receptors of immunological effector cells is a common physiological mechanism; 2) Presence of sIL-2R represents a sign of an overall activation of the effector elements of the host's cellular immune system; 3) An increase in the levels of sIL-2R represents an active phase of progression; conversely, decreasing levels indicate tumor regression; 4) Serum levels of sIL-2Rs may represent a useful laboratory parameter in choosing an efficient anti-cancer therapy. Thus, the level of sIL-2R in childhood solid tumor patients has a prognostic significance.

Cell Transformation, Neoplastic↗
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Telomeres, telomerase and cancer: is the magic bullet real?

Nature recruited telomerase to compensate for the incomplete replication of chromosomal ends (telomeres). In higher organisms, telomeres are eroded at each cell division. Cancer cells frequently show chromosomal instability resulting in ring chromosomes, telomeric associations, and dicentric chromosomes. As a consequence of telomeric erosion, the ribonucleoprotein complex termed "telomerase" is reactive in a subpopulation of cells. Telomerase adds a hexameric repeat of the sequence 5' TTAGGG 3' to the ends of the chromosomes and hence stabilizes the telomeric length. Telomerase is active in vertebrates mostly in germ cells and the early stage embryo but is inactivated or repressed in somatic cells. Detection of telomerase activity in the overwhelming majority of advanced and metastatic human cancers but not in most somatic cells implies that telomerase-dependent immortalization could contribute to the malignancy. Future studies on the expression and regulation of the individual components of telomerase may enable us to clarify the diagnostic and therapeutic potential of telomerase in cancer.

Animals↗
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Immunophenotypically varied cell subpopulations in primary and metastatic human melanomas. Monoclonal antibodies for diagnosis, detection of neoplastic progression and receptor directed immunotherapy.

During a systematic, immunocytochemical screening of 40 human cutaneous melanomas (30 primary and 10 metastatic) for immunophenotype (IP) heterogeneity, we employed a library of 20 well characterized, commercially available mono- and polyclonal antibodies. The use of the sensitive, indirect, four to six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique provided excellent results. The immunocytochemically most characteristic IP for primary cutaneous melanoma, as detected by us was: HMB45+, S-100+, CEA+, vimentin+, cytokeratin 19+, p53+, Rbgene+, nm23+, HLA-DR+, HL.A-DP+, c-erbB3/HER-3+/-, cytokeratin 10/13+/-, HLA-DQ-, cytokeratin 5/8-, EMA-, c-myc-, and actin-. During melanoma progression, a tendency toward poor differentiation (dedifferentiation) and an increase in c-myc expression have both been observed, the latter downregulating HLA-A,B,C expression and consequently diminishing the possibility of melanoma cell Iysis by powerful CD8+, cytotoxic T lymphocytes (CTL) or other cytotoxic cells which requires HLA class I antigens. The development of the metastatic potential in melanomas caused an increase in CEA expression, eliminated the presence of nm23, and prompted the appearance of actin among the intermediate filaments, composing the cytoskeleton of these malignant tumor cells. The most characteristic IP for MMs, identified by this study was HMB45+, S-100+, CEA+, EMA+, vimentin+, HLA-DR+, HLA-DP+, cytokeratin 19+, actin-, c-erbB3/HER-3+, p53+, cytokeratin 10/13+/-, c-myc+/-, c-erbB2/HER-2+/-, HLA-DQ-, cytokeratin 5/8-, Rb gene-, nm23-. It has been observed that adhesion molecules and integrins play a significant role in the complex process of melanoma metastasis and thus we propose a blocking of these de novo expressed molecules with the appropriate antibodies as a form of immunotherapy of PMs and early stages of MMs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
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Immunocytochemical observation of multidrug resistance (MDR) p170 glycoprotein expression in human osteosarcoma cells. The clinical significance of MDR protein overexpression.

Resistance to several cytotoxic agents (MultiDrug Resistance MDR), including anthracyclines, vinca alkaloids and epipodophylline derivatives can occur in human osteosarcoma (OS) cells, detected by the overexpression of a 170 kD glycoprotein (p170), as a result of increased expression of the MDR gene (mdr1). The p170 glycoprotein in normal cells is a membrane transport system protein and its quantitative increase results in increased drug efflux and decreased intracellular drug concentration. Normal renal epithelial cells express p170 as a function of their secretory duties therefore this human tissue was used as a positive tissue control in our immunocytochemical study. This partially retrospective immunocytochemical study was carried out on routine, 10% neutral formalin fixed, decalcified, paraffin embedded, tissue sections of 43 OSs, treated between 1981 and 1993 at the Orthopaedic Hospital of Los Angeles. The immunoperoxidase antigen detection protocol, submitted by Hsu et al (1981) was employed. The search for p170 was carried out with three newly developed monoclonal antibodies (MoABs) (JSB-I, C-219 and C-494, from Signet Laboratories, Dedham, MA 02026). The initial expression of MDR was not detectable in seven OSs. 36/43 OSs expressed p170 on/in their cells. Heterogenous cellular microenvironment and various grades of differentiation features were also determined in the examined OSs. In 17/43 OS cases presence of intensive staining (probably overexpression) of p170 protein was registered. The 43 OSs exhibited different staining patterns with each MoAB. MoAB JSB-I reacted with a transmembranic antigen epitope. The long incubation time with C-219 resulted in heterogeneous cytoplasmic staining. MoAB C-494 also produced an intensive staining mainly localized on the cell membrane of the OS cells. These statistically significant immunocytochemical results suggest a direct correlation between the quantitative presence of p170 glycoprotein in human OS cells and the efficacy of the employed chemotherapy. Future observations employing the in situ hybridization technique will allow the quantitative measurement of the primary or secondary presence of MDR glycoprotein in human OS cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
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Human cancer detection and immunotherapy with conjugated and non-conjugated monoclonal antibodies.

Classical therapeutic modalities such as surgery, radiation and chemotherapy not only fail to cure the majority of neoplastic disease, but their employment also leads to severe and debilitating side effects. The severe cancer related morbidity is often associated with the use of radiation and chemotherapy, making them less than ideal forms of therapy. Entirely new approaches to cancer therapy that are tumor cell directed, and specifically lethal to malignant cells and less toxic to normal tissues are being observed and developed, adhering to the old prayer "Destroy the diseased tissues, preserve the normal." Following the initial advances of Ehrlich, immunotherapy as a fourth modality of cancer therapy has already been developed and proven to be quite effective. Unfortunately, the cancer cell population is not a static entity, but rather a continually changing one. Considerable variations have been determined between individual malignant cells. Our strong belief is that it is necessary for present-day clinical oncologists to become aware of the existence of immunotherapy and learn how to employ it in order to improve the efficacy and decrease the side effects of modern cancer therapy. The development of hybridoma technology and the advances in monoclonal antibody (MoAB) production have revitalized the concept concerning the existence of cancer cell-targeted, specific "magic bullets". In addition, a variety of different agents (e.g. toxins, radionuclides, chemotherapeutic drugs) have been conjugated to mouse and human MoABs for selective delivery to cancer cells. Preclinical observations in athymic, nude mice using xenografted human cancers and mouse, anti-human MoABs were more than impressive and have lead to several clinical trials. Strategies for the employment of MoABs for cancer immunotherapy include: a) Immune reaction directed destruction of cancer cells; b) Interference with the growth and differentiation of malignant cells; c) Antigen epitope directed transport of anti-cancer agents to malignant cells; d) Anti-idiotype vaccines. Phase I studies have established the safety of employing immunoconjugates in humans, but the therapeutic results were less impressive. The clinical use of mouse MoABs in humans is limited due to the development of an anti-globulin immune response to the non-human immunoglobulins by the human host. Genetically engineered chimeric human-mouse MoABs have been developed by replacing the mouse Fc region with the human constant region. Moreover, the framework regions of variable domains of rodent immunoglobulins were also experimentally replaced by their human equivalents. These antibodies can also be designed to have specificities and effector functions determined by researchers, which may not appear in nature. The astonishing immunophenotypic (IP) heterogeneity of cancer cells, the different cytotoxic activity associated with the moiety linked to given MoABs, and mostly the impressive genetic modulation capabilities of cancer cells still remain as yet unsolved difficulties in the present immunotherapy of human cancer. Antibodies with two binding ends (bispecific antibodies) provide a great improvement in targeting cancer cells. The existing inadequacies of MoABs in immunotherapy may also be improved by increasing their efficiency with chemical coupling to various agents such as bacterial or plant toxins, radionuclides or cytotoxic drugs. In writing this review article, one of our main goals is to encourage further clinical research with the use of genetically engineered rodent MoABs and various immunoconjugates in the treatment of human cancer, as well as the combination of such immunotherapy with the three conventional modalities of therapy. Finally, we propose that MoAB-based immuno-therapy be accepted as a conventional form of therapy and employed not only in terminal cancer patients, but also, for instance, during and following surgical resection.

Animals↗
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Identification of neural crest derived cells within the cellular microenvironment of the human thymus employing a library of monoclonal antibodies raised against neuronal tissues.

The organization of optimal microenvironmental conditions within the developing thymus for lymphatic stem cell migration and their further maturation requires cellular and humoral participation of the neural crest. Recently, the immunophenotypical (IP) heterogeneity of lymphatic cells has become a scientific fact. Monoclonal antibodies (MoABs) produced against the various subpopulations of the reticulo-epithelial cells (RE) demonstrated their heterogeneity. We suggest that with a library of MoABs, raised against normal neuronal tissues, neural tumors, and a medulloblastoma cell line, including UJ13/A, UJ127.11, UJ167.11, UJ223.8, UJ308, J1153, A2B5, 215.D11, 275.G7, 282.1, antineurofilament (NF - med. m.w.), and anti-Thy-1 it is possible to recognize cells of neural crest origin within the postnatal thymic cellular microenvironment. Evidence has been collected concerning such connections between the nervous system and the thymus, such as the production of neuropeptides, oxytocin, and neurophysin by the thymus. Our immunohistochemical study was carried out on quick-frozen sections of human postnatal thymuses removed during open heart surgery, employing an indirect, alkaline phosphatase conjugated streptavidin-biotin technique. The employed MoABs reacted with the subcapsular (outer cortex) thymic nurse cells (TNCs) and with medullary RE cells, in close contact with already mature, immunocompetent T lymphocytes ready to leave the thymic microenvironment and enter the peripheral blood. The thymic medulla's strong immunoreactivity with A2B5, which binds to the GQ ganglioside, is typical for peptide secreting cells often migrated from the neural crest. A2B5+, Thy-1+ IP was demonstrated on the large TNCs. Cortical RE cells showed reactivity with UJ127.11, UJ223.8, and UJ308. Dense expression of neural crest antigens was detected in the Hassall's bodies (HBs) employing MoABs UJ223.8, UJ308, 215.D11, and 275.G7. These results suggest a neural crest origin for TNCs and for 20% to 30% of the cells of thymic microenvironment. The outer (peripheral) part of the HBs contained functionally very active RE cells. These RE cells also expressed antigens characteristic of the neural crest, detectable with MoABs UJ127.11, UJ223.8, UJ308, J1153, 215.D11, 275.G7 and A2B5.

Animals↗
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Introduction: human pathology within the broad scope of comparative pathology.

Pathologic integration is the basic phenomenon of comparative pathology. Since man evolved as earth's most influential species, he was unequally influenced the progression and prevention of diseases in himself and other species. This has both positive and negative ramifications. Positive influences have been life-style, the prolongation of life under healthy conditions and medical progress as seen in the treatment of diabetes mellitus, dental hygiene and other factors, such as the decrease of infectious and parasitic diseases, which are still dominating factors in developing nations. Negative influences are side effects of medical treatments, the appearance of occupational, and certain recreational diseases. These are the pathologic effects of man's life-style to which car accidents, smoking and other factors can be added. Different species are affected by environmental changes such as pollution, ozone, acidic rain, polluted food, and transmission of different diseases from one species to another. Interspecies-specifically the direct influence of man in the extermination of other species, or the indirect influence such as through pollutants in the environment producing chain reactions in different species, can be distinguished. The physical environment has been changed as can be seen in air pollution in large cities, the damage to the ozone layer and the increase of malignant melanoma in certain regions of western Australia. The industrialized nations are dominated by non-infectious diseases such as atherosclerosis and neoplasms, whereas in the developing nations parasitic and infectious diseases stand in the fore-front. Particular diseases like acquired immunodeficiency syndrome increase in both types of nations. These diseases may have developed from other species, e.g. the plague which was originally a disease of rodents, especially rats where it was transmitted by the flea, Xenopsylla cheopis, Rothschild. The principle of foremost importance is the disruption of biologic integration of normal processes leading to different types of pathologic progression. A typical problem affecting man and many other fellow species is crowding. Man's pathology and the pathology of other species exhibit continued integration which is the central problem for understanding diseases where similar functions are performed by various structures, such as is the case in gaseous exchange, or differences in size and life span. The broad spectrum of comparative pathology which centers around human pathology provides a source of increased knowledge for a better understanding of diseases. The present issue is based on the two symposia organized by the International Society for the Study of Comparative Ongology during the Fifth International Conference of Anticancer Research, 17-22 October 1995, Corfu, Greece.

Animals↗