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Biomedical subjects

M Reiss

Publications and source records attributed to M Reiss.

At least 145 records · Page 8Linked to original sources

Transforming growth factor-beta in breast cancer: a working hypothesis.

Transforming Growth Factor-beta (TGF beta) is the most potent known inhibitor of the progression of normal mammary epithelial cells through the cell cycle. During the early stages of breast cancer development, the transformed epithelial cells appear to still be sensitive to TGF beta-mediated growth arrest, and TGF beta can act as an anti-tumor promoter. In contrast, advanced breast cancers are mostly refractory to TGF beta-mediated growth inhibition and produce large amounts of TGF beta, which may enhance tumor cell invasion and metastasis by its effects on extracellular matrix. We postulate that this seemingly paradoxical switch in the responsiveness of tumor cells to TGF beta during progression is the consequence of the activation of the latent TGF beta that is produced and deposited into the tumor microenvironment, thereby driving the clonal expansion of TGF beta-resistant tumor cells. While tumor cells themselves may activate TGF beta, recent observations suggest that environmental tumor promoters or carcinogens, such as ionizing radiation, can cause stromal fibroblasts to activate TGF beta by epigenetic mechanisms. As the biological effects of the anti-estrogen tamoxifen may well be mediated by TGF beta, this model has a number of important implications for the clinical uses of tamoxifen in the prevention and treatment of breast cancer. In addition, it suggests a number of novel approaches to the treatment of advanced breast cancer.

Breast Neoplasms↗

Reappraisal of the role of axillary lymph node dissection in the conservative treatment of breast cancer.

PURPOSE: The purpose of this study was (1) to review systemic therapy practice patterns to assess how information regarding nodal status currently influences systemic therapy decisions, and (2) to review long-term outcome of patients who do not undergo axillary dissection compared with patients who do. METHODS AND MATERIALS: For the current practice patterns portion of the study, the records of 292 patients who presented in the past 3 years with invasive breast cancer and underwent conservative surgery were reviewed to determine systemic therapy administered with respect to patient age, primary tumor size, clinical nodal status, and presenting symptoms. For the long-term outcome portion of the study, the records of 955 patients with invasive breast cancer who underwent conservative surgery and radiation therapy before December 1989 were reviewed. Patient characteristics and outcome of those patients who underwent axillary dissection (n = 565, 59%) were compared with a cohort of patients treated during the same era who did not undergo axillary dissection (n = 390, 41%). RESULTS: For the current practice-patterns cohort, information regarding nodal status appeared to influence adjuvant systemic therapy for those patients less than 50 years of age and for those patients with palpable masses who were older than 50. Patients older than 50 with nonpalpable mammographically detected tumors have a low probability of nodal involvement and information regarding nodal status rarely changed therapy in this group of patients. In the long-term outcome study, there were no significant differences in the rates of distant metastasis, disease-free survival, or overall survival between those patients who underwent lymph node dissection and those who did not. CONCLUSION: For selected patients, axillary lymph node dissection appears to have little influence on subsequent management and long-term outcome. These data suggest that it is time to reassess the role of axillary lymph node dissection in patients who undergo conservative surgery and radiation therapy.

Actuarial Analysis↗

Laterality of writing hand in East German samples.

Analyses of distributions of individuals' writing with the left hand and the correlation with handedness in several East German samples (202 children, 299 pupils, 356 students, and 606 adults) indicated the largest correlation for writing hand and handedness was for children. So the writing hand is measurable in children but not in older groups in East Germany.

Adolescent↗

Asymmetry of the stepping test.

The influence of handedness on a measure of the vestibulospinal response was investigated with 25 right-handed and 25 left-handed subjects to examine the asymmetry of the stepping test. Right-handed subjects showed dominance of the right side indicated by direction of movement, but left-handed subjects tended much less to the left side so a functional asymmetry is for left-handers somewhat less clearly expressed.

Adult↗

Lateral preferences in a German population.

There are only a few studies in the literature concerning all four lateral preferences (handedness, footedness, eyedness, earedness) and presenting their interrelationships. Porac and Coren's 1981 inventory was used to assess hand, foot, eye, and ear preference in a German sample of 506 men and 430 women. A right sided preference was found for hand, foot, eye, and ear preference among 91%, 74%, 66%, and 63% of the sample, respectively. More men were left-handed and left-footed than women. There were no significant sex differences for eyedness and earedness. Correlations ranged from .22 between hand and eye laterality to .44 between hand and foot laterality.

Adult↗

Functional importance of hand clasping and arm folding.

The aim of the present study was to investigate the relationship between handedness and hand clasping or arm folding. Our own investigations have shown no relationship as is consistent with most results in the literature which suggests only minor functional importance of these two signs of latent handedness.

Adult↗

Further aspects of the asymmetry of the stepping test.

The test-retest reliability of the asymmetry of the Unterberger stepping test was obtained over a 3-mo. period. This stepping test is a test examining the labyrinthine deviation when testing the lower extremities. Also, self-report items were validated against individual measures of the stepping test. The investigations show high reliability of the asymmetry of the stepping test. The data indicate further that a questionnaire is a valid method for the assessment of the asymmetry of the stepping test.

Adult↗

Transfer of chromosome 18 into human head and neck squamous carcinoma cells: evidence for tumor suppression by Smad4/DPC4.

Cytogenetic, allelotype, and somatic cell hybrid studies of human head and neck cancers had suggested that the long arm of chromosome 18 might carry a tumor suppressor gene locus. To directly test this hypothesis, we introduced a wild-type copy of chromosome 18 into FaDu-Hyg-R head and neck squamous carcinoma cells. Five of 10 chromosome 18 hybrid clones formed invasive carcinomas in nude mice at a significantly lower rate and after a longer latency than the parental tumor cells, whereas the five remaining clones were tumorigenic. These results indicate that tumor formation was suppressed by chromosome 18. A homozygously deleted region of 18q in FaDu-Hyg-R cells included the candidate tumor suppressor gene, Smad4/DPC4, and extended into the DCC tumor suppressor gene locus, but not Smad2/MADR2. Each of the hybrid cell lines carried a full-length donor copy of the DCC gene, independently of their capability to form tumors in vivo. In contrast, each of the hybrid clones that were either completely or partly suppressed carried an intact copy of Smad4/DPC4, whereas this gene was deleted in the two most highly tumorigenic clones. Furthermore, the presence of Smad4/DPC4 correlated with partial restoration of cellular responsiveness to transforming growth factor beta. These results provide strong evidence for tumor suppression by Smad4/DPC4.

Animals↗

Frequent inactivation of the transforming growth factor beta type II receptor in small-cell lung carcinoma cells.

Small-cell lung cancer (SCLC) has a significantly worse prognosis than other forms of bronchogenic carcinoma. Because transforming growth factor beta (TGF-beta) appears to play an important role in the pathogenesis of SCLC, we examined the status of the TGF-beta receptor system in a series of 11 human small-cell carcinoma cell lines. None of these cell lines expressed more than one-tenth the level of TGF-beta type II receptor (T beta R-II) gene mRNA produced by TGF-beta-sensitive normal epithelial cells. In addition, one of the cell lines expressed a second truncated T beta R-II transcript, which is predicted to encode a protein that lacks the terminal two-thirds of the serine-threonine kinase domain. No other structural alterations in the promoter or coding sequences of the T beta R-II gene were found in any of the cell lines, nor could the loss of T beta R-II mRNA expression be ascribed to de novo hypermethylation of promoter/enhancer sequences. These findings indicate that inactivation of the TGF-beta signaling pathway caused by the loss of T beta R-II gene expression is a common and, therefore, probably pathogenetically important feature of small-cell lung carcinoma.

Carcinoma, Small Cell↗

[Endoscopic removal of osteoma of the paranasal sinuses].

Osteomas are benign bone tumors, which are mostly localized in the nasal sinuses. The removal of nasal sinus osteomas, because of their hardness and scope, mostly requires extensive drilling work, which, especially in the case of big osteomas, also makes a large access path necessary. The introduction of endoscopic or microscopic technologies and experiences from the endoscopic opening of the osseous choanal atresias, where extensive drilling deep in the nose is carried out, make the endonasal access possible, even for the removal of nasal sinus osteomas. We treated a 59 year old patient, who, beside a pronounced polyposis of the nasal sinuses, also exhibited a large osteoma in the area of the right ethmoidal labyrinth. In the course of the intranasal sinus operation, the osteoma was completely removed via the same access route. The osteoma had to be gradually minced, intranasally, as it was too large to pass through the piriformes aperture. This approach shows an expansion of our endoscopic possibilities. Additionally, the etiology of the osteoma and its correlation with the polyposis is discussed.

Adolescent↗

[Technical aspects of studying motor asymmetry].

The present review shows the variability assessing motoric asymmetries. There are preference and performance tests. Motoric asymmetries are strongest and most manifest for handedness (hand preference and performance), descending through footedness and other less known asymmetries. A vast range of testing techniques have been used to assess handedness. Writing and self-report are two of the most popular techniques. Other preference measures include observation of how people use tools and questionnaires. Performance test assess speed and accuracy in tasks stressing manipulative dexterity. Although questionnaires are generally thought to be reliable and valid instruments, there is a disagreement as to the nature, the number and weighting of the items to be included.

Brain↗

[Allergic rhinitis--is allergen elimination a useful form of therapy?].

Therapy of allergic rhinitis consists of allergen avoidance, pharmacotherapy, immunotherapy, surgery or a combination. One aspect is the allergen avoidance. The present review discusses some topics and the usefulness of this simple and basic therapy basing on own experiences. When possible, environmental control measures for indoor allergens should be applied if their efficacy is not complete. They may generally improve the patient and reduce the need for pharmacologic treatment. Furthermore, even the allergen source such as a pet is removed from a patients environment, the benefit may take several weeks or month to be perceived. Mite avoidance can be attempted by several methods: reducing the amount of house dust, reducing indoor humidity, by use of miteproof covers and by the application of acaricides. It is more difficult to reduce exposure to pollen and outdoor allergens.

Allergens↗

[Genetic problems of handedness].

The present review discusses the heredity of the most famous and important lateral sign, namely handedness. There are some problems in assessing the handedness and so it is not ever easy to describe the phenotype of handedness in relation to the genotype. Another important point is the biological foundation. It is possible to argue that genes are left-right agonistic. All available family studies on handedness are presented and altogether they show a clear intrafamiliar relationship. Data of adoption studies on handedness are rare but they indicate that the effects of shared biological heritage are more powerful determinants of handedness than sociocultural factors. Several genetic models are discussed shortly favoring the Annett- and the McManus-model because they calculate a directional and a fluctuating asymmetry. Finally the present review describes the factors favoring a genetic influence (presence of asymmetries in infants, structural and behavioral asymmetries) and those favoring sociocultural determination (twin data). The body of data offers substantial evidence for the influence of genes.

Adult↗

Transforming growth factor-beta and cancer: a love-hate relationship?

This commentary proposes the working hypothesis that transforming growth factor-beta (TGF-beta) can play two different and opposite roles with respect to the process of malignant progression. During the earliest stages of carcinogenesis, TGF-beta can act as potent tumor suppressor and may mediate the actions of chemopreventive agents such as retinoids and tamoxifen. However, at some point during the development and progression of malignant neoplasms, bioactive TGF-betas make their appearance in the tumor microenvironment and the tumor cells appear to escape from TGF-beta-dependent growth arrest. Evidence is accumulating rapidly that this TGF-beta resistance is the consequence of inactivating mutations in any one of the genes that encode signaling intermediates, which include the type I and type II TGF-beta receptors, as well as several Smad proteins. The potential implications of the phenotypic switch from TGF-beta sensitive to TGF-beta resistance that occurs during carcinogenesis for cancer prevention and treatment are discussed.

Animals↗

Interferon-inducible protein 10 as a possible factor in the pathogenesis of cutaneous T-cell lymphomas.

Human IFN-gamma-inducible protein 10 (IP-10), a C-X-C chemokine secreted by IFN-gamma-stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits the proliferation of early subsets of normal and of leukemic hemopoietic progenitors. Cutaneous T-cell lymphoma (CTCL) is an indolent lymphoproliferative disorder of CD4-positive lymphocytes that remain confined to the skin for many years before visceral dissemination. Because IFN-gamma mRNA was detected in the epidermis of CTCL lesions, we decided to investigate the role of IP-10 in the epidermotropism of CTCL by determining its expression in normal skin and in CTCL lesions. Using purified recombinant IP-10 (rIP-10) or a recombinant fusion protein between IP-10 and the straight phi10 protein of phage T7, we generated rabbit antisera that recognized and neutralized rIP-10. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal keratinocytes but not by the more differentiated cells. In the often hyperplastic epidermis overlying CTCL lesions, IP-10 immunostaining was enhanced compared to normal skin and extended to the suprabasal keratinocytes in 28 of 29 patients for a frequency of 97% and a 95% confidence interval of 82-100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only 3 of 29 patients (10%; 95% confidence interval, 2-29%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was overexpressed before treatment but was normally expressed at remission. The in vitro proliferation of primary normal human keratinocytes was inhibited in a dose-dependent manner by rIP-10. These results suggest that IP-10 plays a role in the epidermotropism of CTCL. Additional work is needed to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be useful in the development of curative strategies for this disorder.

Adult↗

A mutation in the transforming growth factor beta type II receptor gene promoter associated with loss of gene expression.

Expression of transforming growth factor beta type II receptors (TbetaR-IIs) is either greatly decreased or absent in many tumors, implying that the loss of TbetaR-II function is one of the mechanisms leading to tumor development. In this report, we examine the expression of the TbetaR-II receptor in a squamous carcinoma cell line that expressed reduced levels of TbetaR-II mRNA. We found an A --> G mutation at position -364 of the 5' untranslated region of the TbetaR-II gene. This mutation results in significantly decreased transcriptional activity by the TbetaR-II gene promoter, suggesting that it is a primary mechanism of loss of TbetaR-II expression in this tumor cell line.

Cell Line↗