Biomedical subjects

H E Kaiser

Publications and source records attributed to H E Kaiser.

At least 91 records · Page 5Linked to original sources

PubMedDate not supplied

Invasion and metastasis: the expression and significance of matrix metalloproteinases in carcinomas of the lung.

Structural changes in the extracellular matrix (ECM) are necessary for cell migration during tissue remodeling and tumor invasion. The matrix metalloproteinases (MMPs) and their inhibitors have been shown to be critical modulators of ECM composition and are thus, crucial in neoplastic cell invasion and metastasis. Expression of MMP-2, -3, -9, -10, and -13 was investigated in human lung adenocarcinomas employing an indirect alkaline phosphatase conjugated immunocytochemical technique. Evaluation of the results was based on (a) the percent of neoplastically transformed cells/surrounding stroma that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in lung adenocarcinomas, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells (++++), and the staining intensity was also the strongest possible (A,B). Focal (+), high intensity (A,B) staining could be detected for MMP-2, -9, and -13. Thus, it seems that the stromelysins are involved in the generalized growth and expansion of the neoplastic cell mass, while MMP-2, -9 and -13 are involved in the neoangiogenic and focal clonal selection and expansion phenomena associated with in situ tumor progression, invasion of the microvasculature, and metastasis.

Adenocarcinoma↗

PubMedDate not supplied

Matrix metalloproteinases in neoplasm-induced extracellular matrix remodeling in breast carcinomas.

Structural changes in the extracellular matrix (ECM) are necessary for cell migration during normal and pathologic tissue remodeling and neoplastic cell invasion. The matrix metalloproteinases (MMPs) and their inhibitors have been identified to be critical modulators of ECM composition and are thus, crucial in neoplastic cell progression, invasion and metastasis. Expression of MMP-2, -3, -9, -10, and -13 was investigated in human breast carcinomas (BCs) employing an indirect, biotin-streptavidin based, alkaline phosphatase conjugated immunocytochemical technique. Evaluation of the results was based on (a) the percent of neoplastically transformed cells/surrounding stroma that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D (negative)]. The two forms of stromelysin, MMP-3 and -10, share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in BCs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells (++++), and the staining intensity was also the strongest possible (A). High intensity immunoreactivity (A,B) but focal was detected employing a MoAB targeted against the MMP-9 enzyme. No presence of MMP-2 or -13 could be established in the BC cases observed by us. Based on these results we propose that MMP-3 and -10 are implicated in the pathogenesis of BC, while MMP-9 is possibly involved in neo-angiogenic events also closely associated with growth and expansion of the neoplastically transformed cell mass, as well as metastasis of individual, extremely aggressive, expressing dedifferentiated cellular immunophenotype (IP) cell clones selected during the microevolution of the BC.

Alkaline Phosphatase↗

PubMedDate not supplied

Effects of butaclamol, clopenthixol, mepromazine and cannabinol stereoisomers on apoptosis induction.

The efflux pump of multidrug resistant mdr cells have different sensitivities to some stereoisomeric forms of CNS-active compounds. The ABC transporters of mdr cells were more sensitive to (-)butaclamol than to its stereoisomeric counterpart (8), which may function to alter the membrane structure. We suppose that the drug-accessible membrane structure possesses an important role in the induction (or prevention) of apoptosis. Therefore the apoptosis-inducing effect of three stereoisomeric pairs was studied on mouse lymphoma cells. In these experiments levo- and dextromepromazine had similiar effects. The cis- and trans-clopenthixol were less effective in apoptosis induction than the 12H-benzo(a)-phenothiazine used as a positive control. The effect of stereoisomeric pairs on induced apoptosis was studied when the cells were exposed to the stereoisomers for 60 minutes before subjection apoptosis induction by benzo(a)phenothiazine, a well-known apoptosis inducer. Then the pretreated cells were exposed to 12H-benzo(a)-phenothiazine for 60 minutes. The samples were washed and incubated for 24 hours. The cells were stained with annexin-V-FITC and propidium iodine and investigated by flow cytometry. The mdr cells with increased membrane integrity may result in the preferential killing of multidrug resistant cancer cells in the presence of some stereoisomers.

Animals↗

PubMedDate not supplied

A model of BAX gene delivery to human lung cancer.

In this report we have investigated the effects of BAX in enhancing apoptosis in two primary non-small cell lung cancer cell lines. A count of the apoptotic cells by TUNEL staining revealed that almost 70% of BAX over-expressing cells died, while very few apoptotic cells were detectable in the wildtype cells or in the cells transfected with an empty vector. These findings suggest that de-regulated expression of BAX may provide a novel mechanism for initiating cell death in non-small cell lung cancer cells. Further studies are needed to better define the involvement of this protein in the complex mechanism of lung carcinogenesis and to definitely demonstrate the therapeutic utility of targeting this pathway.

Apoptosis↗

PubMedDate not supplied

COX-2, NSAIDs and human neoplasia. Part I: Colorectal neoplasms.

Cyclooxygenase-2 (COX-2), the inducible cyclooxygenase isozyme involved in the conversion of arachidonic acid (AA) to biologically active prostanoids, has become the subject of intense interest during the last few years. The recent surge of interest stems from seminal studies that correlated elevated expression of COX-2 with tumor induction and progression, and epidemiological studies that correlated reduced risk of developing certain types of cancers with chronic use of non-steroidal anti-inflammatory agents (NSAIDs). Although these observations were first reported with colorectal cancer (CRC), similar findings have subsequently been made with other types of cancers. A wide spectrum of studies continue to be undertaken in both laboratory and clinical settings to elucidate the mechanisms underlying these anti-tumor effects of COX-2 for potential translation into cancer chemoprevention and therapy. The aim of this article is to present a review of COX genes, the prostaglandin-cyclooxygenase relationship, the role of COX-2 in carcinogenesis and the rationale for targeting COX-2 with NSAIDs for cancer chemoprevention. Special emphasis is given to the role of COX-2 expression in the genesis and progression of colorectal neoplasia, and its correlation with other pathological characteristics of CRC. Preliminary observations on COX-2 expression in inflammatory bowel disease (IBD)-related colorectal neoplasia are also presented.

Adenoma↗

PubMedDate not supplied

Preneoplastic lesions of the prostate-clinical, pathological and molecular biological aspects.

Needle biopsy is the mainstay of definitive diagnosis of prostate cancer (PCA). While prostate-specific antigen (PSA) screening has facilitated early diagnosis of PCA, it has also resulted in an increase in the proportion of prostate biopsies showing various preneoplastic lesions (PNLs). At times such lesions are the sole finding in the limited amount of tissue available for assessment in an individual biopsy. Hence accurate identification of these lesions is important to avoid errors in the diagnosis of prostatic malignancy and in patient management. Furthermore, some interesting observations have been made regarding the molecular biological aspects of various PNLs during the last decade. In parallel with anatomic and physiological differences in various human races, racial differences have also been observed regarding the incidence of prostatic intra-epithelial neoplasia. This review focuses on prostatic intraepithelial neoplasia (PIN), atypical adenomatous hyperplasia (AAH) and atypical prostatic glands or atypical small acinar proliferation (ASAP) as putative preneoplastic lesions of the prostate. These lesions are reviewed with reference to their overall incidence, histopathological findings, histological differential diagnosis, clinical significance and molecular biological aspects.

Biopsy, Needle↗

PubMedDate not supplied

Expression of proline-directed protein kinase, (p34cdc2/p58cyclin A), a novel cell proliferation marker in childhood brain tumors.

The presence of two proteins of the proline-directed protein kinase (PDPK), the catalytic subunit p34cdc2 and the regulatory subunit p58cyclin A was determined in seven primitive neuroectodermal tumors (PNETs), three choroid plexus neoplasms and eleven astroglial tumors. The highest expression was registered in the cellularly undifferentiated PNETs and glioblastoma multiforme from the astroglial malignant group. Rabbit immunoantiserum against the two subunits of PDPK, a cell proliferation marker, was employed to detect proliferation activity in childhood brain tumors. The PDPK activity was present from Gl- to M-phases in 21 childhood brain tumors with different central nervous system (CNS) localization and cellular atypia. Immunocytochemical analysis employed an indirect, alkaline phosphatase conjugated biotin-streptavidin antigen detection technique on frozen and routine, formalin-fixed and paraffin-wax-embedded tissue sections of brain tumors. We compared the proliferation activity in the cells of normal, morphologically changed and neoplastically transformed choroid plexus. The average proliferation activity was low in comparison with other tissues. The results in normal and neoplastically transformed choroid plexus were very similar. The lowest proliferation activity in the astroglial group belonged to pilocytic ASTRs. The use of cell differentiation as a prognostic factor in primary brain tumors has already been established and is strongly suggested by our research group. Further systematic neoplasm studies and regular employment of these two polyclonal antibodies for immunocytochemical screening experiments are necessary to determine their true diagnostic and prognostic significance.

Adolescent↗

PubMedDate not supplied

Value of multilevel sectioning for improved detection of micrometastases in sentinel lymph nodes in invasive squamous cell carcinoma of the vulva.

UNLABELLED: Clinical usefulness of sentinel lymph node (SLN) biopsy has been demonstrated in the management of early vulvar cancer. However, what constitutes a negative SLN has not been well defined. Furthermore, to what extent the SLNs should be sectioned for the greatest likelihood of detection of micrometastases and whether multilevel sectioning will further increase this detection rate in this setting have not been well studied. We analyzed 280 groin lymph nodes (SLNs=45, non-sentinel [NSLNs]=235) in 14 patients with invasive squamous cell carcinoma (ISCC) of the vulva treated with vulvectomy and inguinal SLN and NSLN dissection at the H. Lee Moffitt Cancer Center (HLMCC) between 1996 and 2001. Each SNL was evaluated for micrometastases by H&E and pancytokeratin AE1/3 (CKAE1/3) immunohistochemical staining. All negative SNLs (N=40) were sectioned times 3 (x3) at 50-micron intervals and independently reviewed by two pathologists in order to assess the utility of this inexpensive and logical approach to identifying additional micrometastases. Also, the Wilcoxon Rank Sum Test was used to determine if there was an association between tumor size, depth of invasion and SNL status. The patient age ranged from 35 to 81 years (mean 59 yrs); size of invasive tumor from 1.0 to 7.0 cm (mean 3.4 cm); depth of invasion from 3 to 25 mm (mean 10.8 mm). Of 45 SLNs examined from 14 patients, 11% (5/45) SNLs were positive for micrometastases on initial H&E and/or CKAE1/3 stains. Eighty-nine per cent (40/45) SNLs were negative in the remaining 9 patients. None of the latter 40 SNLs showed micrometastases on additional multilevel sectioning. Instead 3 of 135 NSLNs examined in these 9 patients revealed micrometastases on H&E (skip-micrometastases). Mean tumor size (cm) and depth of invasion (cm) were 4.06 (s.d. 1.89) and 1.20 (s.d. 0.35) for SLN (+) and 3.02 (s.d. 2.12) and 1.01 (s.d. 0.86) for SLN (-) tumor subsets (p values 0.385 and 0.348, respectively). CONCLUSION: Following routine H&E and CK AE1/3 stains, multilevel sectioning does not appear to detect additional micrometastases in sentinel lymph nodes in squamous cell carcinoma of the vulva. Even though mean tumor size and depth of invasion were greater in SNL (+) as compared to SLN (-) tumor subsets in our series, this difference did not reach statistical significance.

Adult↗

PubMedDate not supplied

Comparative aspects of the quality of life in cancer patients.

Chronologically, neoplastic diseases can be divided into two categories of which the first includes the fast and aggressive disease groups which exhibit a short course after the diagnosis has been established and the second those with dormancy or a slow path of which the development extends over years, even decades. The developed treatment modalities have even expanded the time duration of both groups, and thus cancer has become a group of chronic diseases in many cases. This requires a special adaptation in regard to the life style and quality of the cancer patient. The assessment of the quality of life in the cancer patient has been evaluated through questionnaire to relatives and friends as well as through social experience with cancer patients. The diversity of the disease group is reflected in the need for a more heterogeneous improvement of life style and its quality according to the need of the patient groups. A distinction can be made between acute and chronically ill pediatric patients, the cancer patient who is able to continue his work, the outpatient not requiring hospitalization, the patient with the need for hospital care (for a shorter or longer Period), the hospice patient, the elderly patient, and the terminally ill patient as well as the patient in the last days of life. In a study of 1,227 elderly decedents in Fairfield County, Connecticut, for which 260 respondents reported cancer as the cause of death, approximately 1/5 were reported to have been in moderate or severe pain six hours before death, with little change from the previous month.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMedDate not supplied

The possible role of the initial lymph vessels of the skin during metastasis of malignant tumors.

The metastasizing potential of a malignant tumor is derived primarily from its biological characteristics. The second most important factor in metastatic spreading lies in the host tissue/organ and host metabolism. The aggressiveness of a malignant skin melanoma depends clinically upon the width and, especially, the depth of the preceding lesions(s). Histological and electron microscopic studies reveal that the increase of malignant aggressiveness is directly related to the arrangement of the initial lymphatic vessels in the different layers of the skin. Sudden increase in the density of lymphatic vessels permits a corresponding increment of malignant seeding via the lymphatic system.

Humans↗

PubMedDate not supplied

Comparison of arteriosclerosis, neoplasms and diabetes as the three main killers of man in the industrialized world.

Arteriosclerosis, neoplasms and diabetes are the three main killers in the industrialized world, complemented by infectious and parasitic diseases in the less developed countries. Neoplasms, the second most frequent killer in the industrialized world, exhibit the highest diversity of pathologic structures involved. Arteriosclerosis, the first killer in the industrialized world, is more complex, dealing with aberrations of the arterial wall. In contrast to neoplasms, cases are restricted to a closed circulatory system as noted in the various phyla. Neoplasms are also known from the kingdom of plants and fungi, whereas arteriosclerosis is restricted to specific animal phyla, at least theoretically. Even more restricted is the distribution of diabetes which is known only in certain vertebrates. All three disease groups have a substantial impact on man's health.

Animals↗

PubMedDate not supplied

Changes in the course of cancer.

Many neoplasms cannot be cured but the life span of the patient afflicted with such diseases has in a remarkable number of cases been prolonged. The course of neoplastic diseases has been changed, improving life-style and survival on the one hand, but resulting in new side effects including multiple primary neoplasms on the other. In contrast to neoplastic diseases with aggressive acute development, we can observe an increasing number of neoplastic diseases with a chronic, prolonged that progress. To understand this it is necessary to remember that neoplastic diseases are heterogenic in nature, and also diseases of autonomic growth comprising modification of the host along with progression of the tumor.

Female↗

PubMedDate not supplied

Some characteristics of the mesenchymal stem cell of soft tissue tumors.

"Soft tissue tumors" is an unnatural term, used by clinicians and for convenience by pathologists, which unites the neoplasms of mesenchymal origin as opposed to those of the soft epithelial tissues. Not included are the reticuloendothelial system, glia and supporting tissues. The mesenchymal stem cell, the cell of the embryonal connective tissue, exhibits in man and mammals the most pronounced embryonal potential. A restricted comparison to the embryonal potential in larval and pupal cells of invertebrates, such as in hemi- or holometabolic insects and to meristematic cells in vascular plants is justified. The great embryonal potential may explain why the mesenchymal stem cell, at present a hypothetical unit, is able to transform and differentiate into the connective tissue as such, the muscular, supporting and hematogenic tissues. The musculature comprises the bulk of the mammal's body weight. The development of the normal ontogenetic specialization as well as especially those differentiations leading to soft tissue tumors are comparatively shown in this publication and placed in the framework of vertebrate and invertebrate animals with true tissues.

Animals↗

PubMedDate not supplied

Cancer growth and progression in the framework of comparative oncology. A new approach to cancer therapy.

The influence of comparative oncology is most timely in view of the fact that there are significant intra- and interspecies differences in tumor development, tumor behavior and tumor reaction to various types of treatment, chemotherapy, radiotherapy, immunotherapy and multimodality-therapy. A comparison of the diverse processes which occur under normal, physiological, neoplastic and therapeutic conditions will result in a clearer understanding of tumor growth and progression. Similarly, it can be applied for selection of suitable treatment by enriching our knowledge about the progression of neoplastic diseases. Such a course will also enhance a general acceptance of the value of comparative oncology.

Animals↗

PubMedDate not supplied

Cancer: causes, prevention, control and treatment (introduction).

Growth is one of the most complicated phenomena of life in its heterogeneity composed of the cooperation of myriads of single processes. This is exemplified by the realization that there exists not one cause of cancer but several groups often ethnically influenced. Species-specific variations occur during the neoplastic development, which exhibits two main phases: I. The change of body metabolism leading via the malignant transformation to a primary tumor; II. The further progression of the neoplastic disease. This introduction, as a brief review, deals with the first phase of neoplastic development examining as causative factors, environment and diet on a comparative approach; to this first phase also belong the cancer causing therapies of nonneoplastic diseases.

Diet↗

PubMedDate not supplied

Bio-immunotherapy for cancer in experimental studies and clinical application: current status and future challenges.

Although successful treatment of patients with primary tumor by conventional surgery and radiotherapy is often possible, death frequently results from tumor metastases. Since metastasis has already occurred in many cancer patients at the time of diagnosis, a major emphasis of cancer treatment is and will continue to be the prevention or successful management of tumor metastases. Systemic chemotherapy has been widely used in the past in the hope of preventing or controlling micrometastases. The results of this treatment have been disappointing with little impact on survival in the vast majority of solid tumors. Bio-immunotherapy has emerged as another modality and is finding acceptance and use in treating patients with cancer. The role of bio-immunotherapy in traditional surgery, radiotherapy, chemotherapy and hyperthermia will be discussed. In order to evaluate new and innovative treatments, we and others have used murine models of erythroleukemia and solid tumors with metastatic potential to assess the effects in vivo of bio-immunotherapy. Tumor metastases can be dampened and immunosuppression restored by bio-immunotherapy, especially when used in combination with other forms of treatment. Most of the combination treatments used in animal models are encouraging but are by no means totally adequate or curative yet. The molecular basis of cancer is now understood to involve activation of dominant oncogenes and inactivation of tumor suppressor genes. These genetic events may represent novel targets for cancer treatment. The potential use and ethical implications of gene transfer to alter the behavior of somatic cells in patients with cancer has been noted. Also reported is genetic immunomodulation by introducting genes for cytokines into tumor cells or lymphocytes to stimulate a cytotoxic immune response against the tumor. As with bone marrow, human cord blood can be used for transplantation in the autologous, related allogeneic and unrelated allogeneic settings, and as a target cell for gene treatment. It is believed that the greatest therapeutic results of bio-immunotherapy, including biological response modifiers, cytokines, gene treatment and bone marrow transplantation, will come in combination with other established effective modalities including surgery, radiation treatment, chemotherapy and hyperthermia in the treatment of patients with cancer.

Animals↗

PubMedDate not supplied

Treatment of circulating neoplastic cells.

The differentiation of tissues and organs during ontogeny increases the necessity of integration of the different structures. These developmental processes of integrations by body fluids, immunologic, endocrine and nervous systems culminate in mammals, since they possess the most diversified system of body fluids. Typical of the most developed mammals are the bone marrow, the lymphatic system with regional lymph nodes and consequently the pathologic development of the diversity of leukemias, malignancies without stroma. In the German literature the leukemias are considered systemic diseases because the floating cells they discharge are more or less uniformly pathologically underdeveloped. The leukemias are named according to the major abnormal cell type (e.g. monocytic acute leukemia). Acute and chronic is the distinction of the time limitation regarding the development and duration of the disease. More complicated is the discharge of motile cells from primary tumors or daughter tumors deriving from solid tumors. These motile cells enter into the circulation via the lymphatic spaces or by penetration of the endothelium of the blood vessels. They move freely in the circulatory system until settling in a more or less distant region. The process of detecting these cells is known as carcinocythemia. Other movable cells during neoplastic progression are those populating effusions in the coelomic cavities. Non-movable, that is only growing in succession like a tissue chain are those tumors which distribute by direct tumor spread within the veins, keeping the connection with the primary tumor. This condition is especially well-known in renal cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Cancer related syndromes from a comparative viewpoint.

Neoplasms are the most prominent portion of the neoplastic disease process. The cancer patient is affected by hormonal, metabolic, immunologic and paraneoplastic discrepancies. Paraneoplastic syndromes consist a large group of body abnormalities which appear in a specific manner. Why special components of such abnormalities occur together is nearly always unknown. This article gives a tabulation of the paraneoplastic and other neoplasia-related syndromes providing certain key characteristics in each case.

Adult↗