Showing papers in "Cancer treatment and research in 1991"
TL;DR: The importance of stromal-epithelial interactions is reemphasized by several models of carcinogenesis that suggest that perturbations in these interactions may be involved in tumor progression.
Abstract: Stromal influences upon epithelia are part of a continuum of cellular interactions that begins at fertilization and extends into adulthood In parenchymal organs, the most thoroughly characterized interactions have been those that occur during development between mesenchyme, embryonic stroma, and epithelium Mesenchyme is essential for epithelial proliferation, morphogenesis, and differentiation Hormones affect stromal-epithelial interactions, and in some cases, steroid hormones may produce their effects on the epithelium indirectly, acting via the mesenchyme In many adult organs the epithelia continually proliferate and differentiate and consequently may be considered developing systems within the mature organism This is especially true in organs with a rapidly renewing epithelium, such as the intestine, and in organs that have cycles of functional activity, such as those of the female reproductive system The mechanisms by which stroma affects epithelial structure and function are not well understood Current models of how signaling may be accomplished include transmission via diffusible substances, via the extracellular matrix (ECM), and via direct cell—cell contact Growth factors and organ-specific paracrine factors are candidates for stromal cues that affect the epithelium in some systems Components of the ECM appear to play a role in permissive interactions and may affect epithelial function by changing cell shape or by binding ECM to the cell surface integrin receptors Signaling via direct stromal-epithelial contact may be accomplished via interactions between complimentary cell surface adhesion molecules The importance of stromal-epithelial interactions is reemphasized by several models of carcinogenesis that suggest that perturbations in these interactions may be involved in tumor progression
159 citations
TL;DR: It is proposed that the IGFs are important stimulators of breast cancer cells and that their growth promoting effects may be mediated by autocrine, paracrine, or endocrine mechanisms.
Abstract: The ability to grow breast cancer cells in vitro has lead to the identification of several polypeptide hormones that may regulate their growth. The insulin- like growth factors (IGFs) have been identified as potent mitogens for breast cancer cells in vitro and increasing evidence has suggested that the IGFs may have an important function in the proliferation of mammary epithelia. This chapter will examine the data that support a role for the IGFs in regulating the growth of breast cancer cells.
64 citations
TL;DR: In breast and other cancers, the HER2 protooncogene appears to play an important role in the development and progression of these diseases, and represents a potential focus for therapeutic intervention.
Abstract: It is by now clear that the pathogenesis of human cancer involves the aberrant functioning of the products of oncogenes. In breast and other cancers, the HER2 protooncogene appears to play an important role in the development and progression of these diseases. As such, it represents a potential focus for therapeutic intervention.
51 citations
TL;DR: Evidence is beginning to accumulate in support of a major role for tyrosine kinase receptors (and their activating growth factors) and steroid hormones and their receptors in normal development and differentiation of the mammary gland.
Abstract: Breast cancer afflicts 1 in 9 women in North America. It is characterized by a strong dependence on intact ovaries for onset and progression in women of all ages, but it is primarily a postmenopausal disease. This appears to be because prolonged exposure of the gland to ovarian hormones is required, but the disease is usually associated with a long latency of 20 years or more [1]. Excessive proliferation, dedifferentiation, genetic mutability, and metastases characterize the disease when it is clinically manifest. It is not yet known what defects occur early in the disease process, but ovarian hormones appear to be critical. The proliferation of the normal gland predominates in the luteal phase of the menstrual cycle, implicating an interaction of both estrogen and progesterone, which are present in this phase. In premenopausal disease, estrogen appears to be the ovarian hormone of primary importance. In postmenopausal breast cancer, when blood levels of estrogen and progesterone are extremely low, breast tumors appear to arise under control of other factors, among which are estrogen synthesized peripherally by aromatase and sulfatase mechanisms. Likely candidates for additional factors regulating breast proliferation and tumorigenesis are locally acting growth factors, genetic alterations of protooncogenes, and aberrant interactions of stromal and epithelial compartments [2]. A very interesting observation is that of the most common oncogene activations in breast cancer (c-erbB-2 and c-myc oncogene amplifications), c-myc amplification is associated with postmenopausal breast cancer. While c-erbB-2 amplification is associated with poor prognosis of breast cancer, irregardless of menopausal status, c-myc is not of strong prognostic significance. This suggests that c-myc may function in premalignant changes and early in tumor progression and that c-erbB-2 might be particularly important later in the progression [3]. This article will focus on the possible mechanisms of action of c-myc in early stages of malignancy. We will address the hypothesis that c-myc may act, in part, by synergistic transforming interaction with growth-factor receptor tyrosine-kinase activities. This mechanism will be contrasted with that of c-erbB-2 amplification, which may act on its own, in the absence of c-myc amplification, to drive other aspects of the cancer phenotype later in malignant progression.
50 citations
TL;DR: Gene rearrangements are observed at low frequency, but there are a proportion of human cancers that are associated with c-erbB2 gene amplification and membrane protein overexpression, with up to 20% of primary lesions exhibiting either increased gene copy number and/or excess membrane staining.
Abstract: There is no evidence for activation of c-erbB2 by mutation in human cancer. Gene rearrangements are observed at low frequency, but there are a proportion of human cancers that are associated with c-erbB2 gene amplification and membrane protein overexpression. The human cancers so affected are adenocarcinomas of the breast, ovary, stomach, and bladder, with up to 20% of primary lesions exhibiting either increased gene copy number and/or excess membrane staining. The c-erbB2 protein on these tumors could be used as a therapeutic target, as in monoclonal antibody targetted therapy already being assessed in c-erbB2 positive breast cancer. Other possible therapeutic strategies include the development of tyrosine kinase inhibitors or ligand antagonists.
47 citations
TL;DR: The goal in this chapter is to discuss the actions of compounds that can modulate Pgp-MDR and some of the ongoing clinical studies with these agents, as well as their attendant problems.
Abstract: Multidrug resistance associated with overexpression of P-glycoprotein (Pgp-MDR) is a well-documented experimental phenomenon whose pharmacologic, biochemical, and molecular basis is known. Its importance resides in the fact that it appears to have clinical correlates, so attempts to reverse or circumvent Pgp-MDR clearly assume high priority. There is a considerable body of experimental work showing that certain classes of membrane-active drugs are capable of circumventing MDR to varying degrees, but it remains to be seen whether these agents will be useful clinically. The goal in this chapter is to discuss the actions of these modulators. The general features of Pgp-MDR will be briefly outlined and its and differences from other forms of MDR recently described will be highlighted. The main focus will be on compounds that can modulate Pgp-MDR. Our current understanding of the mechanism(s) by which these agents work in MDR cells will be summarized, current models for modulator design will be discussed, and some of the ongoing clinical studies with these agents, as well as their attendant problems will be outlined. The conclusion offers some thoughts about future directions of modulator studies.
45 citations
TL;DR: These observations demonstrate that multiple mechanisms of resistance exist, and often several may occur in the same cell line, and hopefully will facilitate improvements in therapeutic response.
Abstract: Cisplatin has become a major clinical drug because of its proven efficacy against many tumors. It exhibits excellent activity against testicular tumors and is responsible for remission rates of about 50% in ovarian cancer. It is also used in combination chemotherapy for a variety of other tumors. As with all anticancer drugs, many tumors are inherently resistant to the therapy or acquire resistance after an initial treatment. Because of the high remission rate in ovarian tumors, this disease has become noted for the high incidence of recurrent tumors. It is quite possible that the mechanisms of inherent and acquired resistance are one and the same, but evidence for this requires further research.
44 citations
TL;DR: The mammary gland is an appropriate system with which to study mechanisms that control gene expression during both growth and differentiation, since following the onset of pregnancy, epithelial cells in the mammary glands proliferate and differentiate into milk-secreting cells.
Abstract: The mammary gland is an appropriate system with which to study mechanisms that control gene expression during both growth and differentiation. It is one of the few tissues with a developmental potential after birth, since following the onset of pregnancy, epithelial cells in the mammary gland proliferate and differentiate into milk-secreting cells. A schematic cross- section of one of the ten mammary glands of the mouse shows the gross changes in structure that occur during progression of the gland in pregnancy (figure 1, upper panel), from the virgin state (V) to lactation (L). During pregnancy (P), certain epithelial cells lining the ducts (which themselves are embedded in stromal tissue) proliferate and form alveolar buds. By the time of parturition, cells in the alveoli become secretory and occupy the entire gland. This structural development is accompanied by the onset of lactogenic function, in which expression of milk proteins begins during pregnancy and culminates with the secretion of milk after parturition [1]. The steady-state levels of the mRNA for β—casein (figure 1, lower panel) illustrate this type of progression with no expression in the virgin state, some during pregnancy, and the highest levels at lactation. After weaning when the gland involutes, β—casein expression is down regulated (figure 1, lower panel, lane I).
41 citations
TL;DR: The available data concerning the possible role of these enzymes and plasminogen activators in tumor development and metastasis are summarized.
Abstract: In recent years, significant progress has been made in understanding the structure, function, and regulation of gene expression of secreted metalloproteinases that participate in the degradation of the mammalian extracellular matrix (ECM). At the same time, several lines of investigation have produced circumstantial evidence implicating these proteases in tumor growth, invasion, and metastasis. A more detailed discussion of the properties of these proteases is outside the scope of this review, but we summarize here the available data concerning the possible role of these enzymes and plasminogen activators in tumor development and metastasis.
39 citations
TL;DR: Evidence for the importance of loss of negative regulation in tumorigenesis has been provided by the identification and characterization of ‘tumor suppressor’ genes, exemplified by the retinoblastoma gene, where loss of both alleles leads with high frequency to the development of a particular malignancy.
Abstract: Cell proliferation is normally controlled by the opposing actions of growth stimulators and growth inhibitors. Regulated changes in this balanced system determine the rate of tissue growth during embryogenesis, and later in response to damage or altered functional demand. The negative autocrine hypothesis proposed that any defect in a normal autocrine growth-inhibitory loop could lead to tumor formation in the affected cell type by upsetting this balance [1]. The mechanistic underpinning of this hypothesis lies in the fact that cellular proliferation is a prerequisite for the fixation of deleterious mutations, and thus for tumor promotion and malignant progression [2]. Evidence for the importance of loss of negative regulation in tumorigenesis has been provided by the identification and characterization of ‘tumor suppressor’ genes, exemplified by the retinoblastoma gene, where loss of both alleles leads with high frequency to the development of a particular malignancy [3].
38 citations
TL;DR: The hypothesis that estrogens and antiestrogens regulate breast cancer progression and tumorigenicity indirectly by inducing the expression and secretion of polypeptide growth stimulators or inhibitors, which then bind and act on breast cancer cells in an autocrine fashion is proposed.
Abstract: It is generally accepted that the induction and maintenance of breast cancer is, at some point and to a variable degree, under control by estrogen. However, the mechanisms by which estrogen regulates the proliferation of human breast cancer cells remain speculative. Recently it has been reported that breast cancer cells can synthesize and secrete a number of polypeptide growth factors or growth factor-like activities, including transforming growth factors alpha and beta (TGF—alpha and TGF—beta), the insulin-like growth factors I and II (IGF—I and IGF—II), platelet derived growth factor (PDGF), and the protease cathepsin D. For some of these growth factors, specific cell surface receptors have been identified in breast cancer cells. Furthermore, addition of exogenous growth factors to these cells under serum-free conditions induces growth stimulation (TGF-alpha, IGF-I, IGF-II, and cathepsin D) or growth inhibition (TGF—beta). Interestingly, the synthesis and secretion of these growth factors are regulated by estrogens and anti-estrogens in some estrogen receptor (ER)-positive hormone-dependent cells, whereas higher levels are expressed constitutively in some ER-negative hormone-independent cells. These data have led to the hypothesis that estrogens and antiestrogens regulate breast cancer progression and tumorigenicity indirectly by inducing the expression and secretion of polypeptide growth stimulators or inhibitors, which then bind and act on breast cancer cells in an autocrine fashion [1]. On the other hand, the growth advantage associated with hormone-independent breast cancer cells may be due to the high constitutive expression of autocrine growth factors.
TL;DR: For example, pieces of immunoglobulins or fragments of oligonucleotides have been used as probes to demonstrate the presence and location of their molecular partners in both cells and tissues.
Abstract: The enormous progress in immunology and molecular biology has encouraged the development of many ingenious techniques that now make it possible to analyze various biological phenomena at the molecular level. For example, pieces of immunoglobulins or fragments of oligonucleotides ]have been used as probes to demonstrate the presence and location of their molecular partners in both cells and tissues. Such capabilities represent an important advance in cell biology and in the fields of animal biology and pathology, where a large amount of knowledge has already been accumulated.
TL;DR: Clinically significant breast tumors are a complex and heterogeneous mix of epithelium, stromal cells, matrix proteins, and vascular elements that requires complex but poorly understood interactions between these various tumor elements.
Abstract: Breast malignancies are almost exclusively epithelial cancers. Epithelial cells that have undergone malignant transformation arise from ductal or lobular elements within the breast parenchyma. However, no breast cancer can grow beyond the microscopic level simply as a proliferation of malignant epithelium. Clinically significant breast tumors are a complex and heterogeneous mix of epithelium, stromal cells, matrix proteins, and vascular elements. The growth and dissemination of a breast cancer requires complex but poorly understood interactions between these various tumor elements. To grow beyond the microscopic level, a tumor must acquire a blood supply. To acquire invasive or metastatic potential, a tumor must be able to manipulate and degrade surrounding basement membrane and intercellular matrix to escape into lymphatic or vascular channels. These same properties may be necessary for a metastatic tumor focus to develop at a distance from the primary tumor.
TL;DR: The combination etoposide, leucovorin, and 5-FU (ELF) in a phase II trial in elderly patients and in patients with cardiac risks who could not be treated with anthracyclines makes this combination a valuable alternative to anthrACYcline-containing regimens.
Abstract: Surgery is the treatment of choice in localized gastric carcinoma. Despite the availability of extended surgical procedures (e.g., gastrectomy, lymphadenec-tomy), the majority of patients with gastric cancer fail surgical treatment. This applies especially to patients with stage III and IV disease who represent more than two thirds of the cases at diagnosis. The 5-year survival rate in stage III disease is less than 15%; in stage IV disease, long-term survival is rare [1]. In addition, the median survival time of patients with advanced gastric carcinoma is short. After potentially curative resection of localized stage III/IV gastric carcinomas, the median survival is approximately 8 months, and after palliative resection, 4–6 months [1]. For patients with unresectable tumors, the outlook is dismal, with median survival being only 4 months [2]. Therefore, other treatment modalities, especially systemic chemotherapy, have been investigated intensively.
TL;DR: Although many organs are fully functional before birth, other organs, particularly those of the reproductive system, undergo major morphogenetic changes and cyclic expression of functional differentiation postnatally over extended periods.
Abstract: Mesenchymal-epithelial interactions are critically important during embryonic development for normal organogenesis. These tissue interactions are thought to be reciprocal and are clearly involved in many fundamental developmental mechanisms, such as morphogenetic movement [1–3], cellular proliferation [4–7], and cell death [8]. Although many organs are fully functional before birth, other organs, particularly those of the reproductive system, undergo major morphogenetic changes and cyclic expression of functional differentiation postnatally over extended periods.
TL;DR: The vast clinical literature provides evidence that the major stimulus for growth of breast cancer is estrogen, and treatment with compounds that act via antagonism of estrogen action, i.e., synthetic antiestrogens and perhaps progestins, leads to remission in a high proportion of patients with receptor-positive tumors.
Abstract: Since the initial availability of hormone-responsive human breast cancer cell lines in the early 1970s, many studies have shown that the control of proliferation and differentiation in these cells involves complex interactions between steroid hormones, peptide hormones, and growth factors [1]. By contrast, the vast clinical literature provides evidence that the major stimulus for growth of breast cancer is estrogen. The low incidence of breast cancer in females without functional ovaries and in males [2], the importance of menstrual and reproductive history as risk factors [3], the marked arrest of tumor growth following ovariectomy in some patients [4], and reinitiation of tumor growth upon administration of estrogen [5] all support a fundamental role for estrogen in breast cancer progression and growth. Furthermore, the fact that treatment with compounds that act via antagonism of estrogen action, i.e., synthetic antiestrogens and perhaps progestins, leads to remission in a high proportion of patients with receptor-positive tumors adds additional weight to this view [6–8].
TL;DR: Differential expression of mdr genes encoding P-glycoprotein isoforms with distinct properties appears to be a possible mechanism for generating diversity in MDR rodent cells.
Abstract: Since the advent of chemotherapy it has been observed that certain types of cancer are rarely sensitive to treatment with chemotherapy. Other cancers that are initially responsive to treatment eventually become resistant to the treatment regimen being used and to some other drugs as well. Resistance to chemotherapy remains one of the fundamental barriers to curative treatment. The mechanisms by which tumor cells become drug resistant have been under intensive study. It is clear from the accumulated data that drug resistance is a complex phenomenon, including more than one mechanism. Resistance may be caused by a change in one, more than one, facet of drug interaction with a cell, from drug influx/efflux and drug metabolism to drug-target site interactions.
TL;DR: Although chemotherapy can result in the cure of many malignancies, there are many cancers, such as breast cancer and non-Hodgkins lymphoma, that initially may respond to chemotherapy and then relapse either during or after therapy.
Abstract: Although chemotherapy can result in the cure of many malignancies, such as testicular cancer, Hodgkin’ s disease, and childhood leukemias, we are continually faced with the obstacle of tumors that respond poorly to chemotherapy, such as non-small-cell lung cancer and gastrointestinal malignancies. In addition, there are many cancers, such as breast cancer and non-Hodgkins lymphoma, that initially may respond to chemotherapy and then relapse either during or after therapy.
TL;DR: The growth and proliferation of reproductive tissues are dependent upon the effects of a variety of modulatory substances, including the sex steroid hormones estrogen and progesterone, and an increasingly long list of growth factors.
Abstract: The growth and proliferation of reproductive tissues are dependent upon the effects of a variety of modulatory substances, including the sex steroid hormones estrogen and progesterone, and an increasingly long list of growth factors. Like their nonmalignant counterparts, the growth, proliferation, and metastatic potential of breast cancer cells are markedly influenced by these substances.
TL;DR: The cytogenetic analysis of melanocytes derived from four dysplastic nevi and 14 melanomas suggests that deletion or inactivation of a gene on 9p may be a primary event in melanocyte transformation.
Abstract: Cytogenetics has proved to be a useful tool in helping to identify regions of the genome in which genes important in malignant transformation may be located. Several research groups have been studying the cytogenetics of melanoma, and other groups have been studying the molecular changes in transformed melanocytes, but no consensus has been reached on the sequence of events that change normal melanocytes into the aberrant cells found in melanomas. This chapter will review some general background literature (covering solid tumor cytogenetics and the models proposed for transformation) and more specific melanocyte literature, cover briefly the growth of melanocytes, present cytogenetic data from dysplastic nevi and melanomas, and suggest a possible sequence of genetic changes that results in malignancy.
TL;DR: The observation that the overexpression of RB1 suppresses the growth of these tumor cells in vitro is consistent with the clinical observation that retinoblastoma does not occur in children in whom the target cells have already fully differentiated.
Abstract: Cancer is a multistep process involving the accumulation of many genetic mutations. These mutations can be the activation of dominantly acting protooncogenes or the inactivation of growth suppressor genes. The initial evidence for a role of growth suppressor genes in cancer development has come from somatic cell hybrid studies in which stable suppression of the tumorigenic phenotype of the hybrid was shown to correlate with the presence of specific chromosomes [1,2]. The observations that different tumor cells can complement each other in the suppression of the tumorigenic phenotype suggests that different chromosomes are involved in controlling tumorigenic expression in different cancer cells. These conclusions were confirmed by microcell fusion chromosome transfer techniques in which single chromosomes were shown to be able to suppress the tumorigenic phenotype of certain tumor cells [3]. An independent line of evidence for the role of recessive genetic mutations in tumor development has come from the study of familial pediatric tumors. It had been postulated that two mutational events are required for the development of retinoblastoma [4]. In hereditary retinoblastoma, since the germline mutation is present in all cells, a second somatic mutation in the target retinoblast is sufficient to allow for tumor development. Initial cytogenetic data and subsequent restriction fragment length polymorphism (RFLP) studies have provided more precise evidence for the involvement of chromosomal regions 13ql4 in the development of retinoblastoma [5]. The isolation of the retinoblastoma gene, RB1, by us and others, allowed a confirmation of the recessive nature of cancer at a single gene level [6,7]. In hereditary retinoblastoma, where the mutations were detected as a homozygous deletion of the RB1 locus, identical structural changes were readily detected in one of the RB1 alleles in the constitutional cells of the patients [7]. In contrast, in nonhereditary retinoblastoma mutations were found exclusively in the tumor and not in the constitutional cells. These data are consistent with the course of mutational events postulated in the two-hit hypothesis. More interestingly these studies imply that the rate-limiting steps in the development of cancer are the loss of genetic material that has a tumor suppression function. This conclusion is perhaps not surprising. Each of the mutational events in the multistep process of tumorigenesis represents a step that a cell must undertake towards full malignant transformation. While the activation of a protooncogene requires only mutation of one of the two alleles of the gene in a somatic cell, both alleles of a growth suppressor gene must be affected for its complete inactivation. Thus, the rate-limiting steps in tumorigenesis are often the inactivating mutation of growth suppressor genes.
TL;DR: In mammalian cells, few DNA repair genes have been identified; thus, isolation of genes on the basis of DNA-damage inducibility offers an approach to identify genes involved in DNA damage processing.
Abstract: Most organisms can respond to changes in the environment by the induction of a variety of different genes. For example, exposure to elevated temperature, heat shock, leads to the increased transcription (induction) of a number of genes whose protein products, the heat-shock proteins (hsp*), may increase the cellular resistance to heat shock. Another example is the cellular exposure to toxic metal salts, such as cadmium, that leads to the induction of genes whose protein products, like metallothionein (MT), have a protective effect by binding these metal salts. As will be discussed throughout this chapter, exposure of cells to DNA-damaging agents can lead to the induction of a variety of genes. In a manner analogous to other stress responses, the products of DNA-damage-inducible (DDI) genes might be expected to have protective roles against genotoxic stress. This is clearly the case for bacteria, and a brief review of DDI genes in prokaryotes has been included for this reason. In eukaryotes, our understanding of DDI genes is less complete than in bacteria, but some evidence has already been found, particularly in yeast, that some DDI genes encode DNA repair functions. In mammalian cells, few DNA repair genes have been identified; thus, isolation of genes on the basis of DNA-damage inducibility offers an approach to identify genes involved in DNA damage processing.
TL;DR: Should camptothecin analogs prove as active in human clinical trials as animal tests predict, it will be interesting to see if additional mechanisms of resistance emerge from studies in treated patients, and if clinical activity is similar to that demonstrated by campthecin 15 years ago, the issue will be of academic interest only.
Abstract: DNA topoisomerase II (EC 5.99.1.3) is a ubiquitous Mg2+- and ATP-dependent enzyme that exists as a homodimer in eukaryotes (subunit molecular mass 131-180 kDa) and is encoded on human chromosome #17. This enzyme changes the linking number of DNA in steps of two and allows the interconversion of topological isomers of DNA by introducing a transient enzyme-bridged double-strand DNA break. Further details regarding the interaction of type II topoisomerases with DNA can be found in several recent reviews [1, 2, 3, 4, 5, 6]. This enzyme has been purified to homogeneity from human Hela cells [7], Saccharomyces cerevisiae [8], Drosophila melanogaster [9], calf thymus [10, 11, 12], Trypanosoma cruzi [13], mouse leukemia P388 cells [14], Crithidia fasciculata [15], and Chinese hamster ovary cells [16]; and the gene has been cloned and sequenced from Saccharomyces cerevisiae [17], Schizosaccharomyces pombe [18], Drosophila melanogaster [19], HeLa cells [20], and human Burkitt lymphoma cells [21].
TL;DR: The ability of FGF and epidermal growth factor -related molecules to simulate growth of the different mammary cell types in culture correlates with the presence of their high-affinity receptors, and these growth factors are promising candidates for some of the primary effectors of mammary growth in vivo.
Abstract: The mammary gland of nonpregnant mammals is composed of an epithelium embedded in a fatty stroma. The epithelium consists of a branching ductal tree terminating in alveolar buds (ABs) in rats or in terminal ductal- lobuloalveolar units (TDLUs) in humans [1, 2]. The boundary of the epithelium is formed by a basement membrane, on the inner surface of which is a more or less continuous layer of elongated myoepithelial cells possessing smooth muscle-like myofilaments and pinocytotic vesicles [3–6]. One or more layers of cuboidal epithelial cells constitute the core of the ducts, with the inner layer bordering a lumen that is continuous throughout the ductal tree [7]. The luminal, cuboidal epithelial cells have apical microvilli and specialized junctional complexes with associated desmosomes. In the terminal ABs and TDLUs that form distended lobules, the luminal layer is composed of secretory or alveolar cells that synthesize and secrete milk products during lactation [2, 8]. More recently a battery of immunocytochemical probes has been used to define, on a more molecular basis, the cuboidal epithelial cell of the ducts, the epithelial cells of the ABs/TDLUs, the myoepithelial cells, and potential transitional cells [9–11]. These probes have been important in understanding the developmental relationship between the different cell types found in the mature mammary gland.
TL;DR: The proteins that make up the intermediate filaments of mammalian cells have in the last 10 years or so been defined in detail at the biochemical and structural level, while the profile of expression of these proteins has been monitored in a wide variety of cells and tissues as mentioned in this paper.
Abstract: The proteins that make up the intermediate filaments of mammalian cells have in the last 10 years or so been defined in detail at the biochemical and structural level, while the profile of expression of these proteins has been monitored in a wide variety of cells and tissues. The various classes of intermediate filament proteins (IFPs), listed in Table 1, show considerable structural similarities but are antigenically distinguishable, so that monoclonal antibodies can be developed that exclusively recognize a single species. In studying the expression of IFPs at the cellular level, particularly in complex tissues, it is these monospecific antibodies that have proved to be extremely useful.
TL;DR: Cases of gastric cancer seen in the hospital are stage II or more advanced, with an unexplained decrease in its incidence in the United States during the past 50 years.
Abstract: Gastric cancer remains a major cause of cancer death, despite an unexplained decrease in its incidence in the United States during the past 50 years. Despite recent advances in diagnostic methods, many cases of gastric cancer seen in the hospital are stage II or more advanced [1].
TL;DR: Findings provide support for the hypothesis that the clinical effects of the MAbs may reflect activation of host responses against the tumor, and for the role of gangliosides in lymphocyte function.
Abstract: Ganliosides were first described by Ernst Klenk in 1936 as a class of glycolipid-containing sialic acids that were found in brain tissue [1]. It is now known that they are components of cells in most tissues and that they are synthesized by glycosyltransferases in the plasma membrane, Golgi apparatus, and microsomes of cells [1,2]. They appear to serve as receptors for products such as cholera and tetanus toxin [2], viruses [3,4], and hormones, such as thyroid-stimulating hormone [2], serotonin [2], interleukin-2 (IL-2) [5], and interferon [2]. They appear to have an important role in cell membranes in either enhancing [6] or inhibiting signal transduction resulting from receptor interactions with a variety of growth factors, such as epidermal growth factor, fibroblast growth factor, and platelet-derived growth factors [6, 7, 8]. In some tissues they appear to be associated with activation of Ca2+-dependent protein kinases [9] and Ca2+-flux across cell membranes [10].
TL;DR: Although genes encoding caseins and whey proteins have some control mechanisms in common, namely, their mammary specificity, other aspects of their regulation are quite different.
Abstract: Although genes encoding caseins and whey proteins have some control mechanisms in common, namely, their mammary specificity, other aspects of their regulation are quite different. In particular, induction of gene expression during pregnancy and the dependence on steroid and peptide hormones for maxium mRNA accumulation differ between the casein and whey protein genes.
TL;DR: It is suggested that these improved local treatments should be combined with aggressive systemic therapy in order to develop an optimal adjuvant approach to the treatment of gastric cancer.
Abstract: Gastric cancer represents an unsolved problem in oncology, with a majority of patients going on to die of their disease, despite an aggressive surgical approach. This cancer fails its surgical treatment, both at systemic sites and within the abdominal cavity. Autopsy studies have shown that local recurrence rates are extremely high with this malignant process. Approximately 9 out of 10 patients are shown to have local recurrence, with the resection site involved in the recurrent malignant process [1]. Also, at least half of the patients who recur have peritoneal seeding in addition to the resection-site recurrence [2]. These local recurrence rates are more commonly seen in patients with lymph-node-positive disease. Recent reports emphasize that survival is reduced and peritoneal seeding plus local recurrence rates are increased in patients who have serosal invasion [3–6]. These two clinical features — (1) lymph-node positivity and (2) serosal invasion — are the strongest prognostic variables with this disease.
TL;DR: The erbB-2 protein is thought to be a cell membrane receptor for a newly described ligand-gp30 in breast cancer and there is some confusion in the literature about the terminology for erb B-2.
Abstract: Originally described as a homologue of the EGF receptor gene amplified in breast cancer [1], erbB-2 protein is now thought to be a cell membrane receptor for a newly described ligand-gp30 [2]. There is some confusion in the literature about the terminology for erbB-2. In brief, erbB-2, c-erbB-2, and HER-2 refer to the same human gene residing in the long arm of the chromosome 17, which has homology to human EGF receptor gene (c-erbB) [3]. erbB-2 protein, p185erbB-2, or p185HER-2 refer to the transmembrane receptor protein translated from the erbB-2 gene, which has a molecular weight of 185 kDa. c-neu refers to the rat counterpart of the erbB-2 gene [4].