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PubMed1998

Identification and characterization of the inducible murine mast cell gene, imc-415.

Activation of mast cells results in the generation and release of bioactive mediators which in turn initiate allergic inflammation. Mast cell function is enhanced following stimulation in part because of the induction of specific genes and their products. To identify additional genes induced in mast cells that support this process, we thus constructed an activation-specific mast cell subtraction library. To date, we have isolated 26 novel inducible murine mast cell (imc) cDNA clones. Among them, a full-coding region of the murine gene imc-415 was found to have a greater than 90% nucleotide sequence homology and a 97.5% amino acid sequence homology to both a human beta4 integrin-binding protein (p27(BBP)) and a human translation initiation factor 6 (eIF6), which in turn are identical. In vitro translation of the imc-415 gene yielded a band of an approximately 26 kDa. This is the same as the calculated molecular weight of murine IMC-415 protein based on the predicted amino acid sequence and is the molecular weight of p27(BBP)/eIF6. Murine imc-415 message was also induced in inflamed lung tissues in a mouse model of asthma. These results suggest a role for murine imc-415 in allergic inflammation where it may enhance protein synthesis. Human eIF6/p27(BBP) may also play a role in allergic diseases based on the similarities in sequence and in gene expression patterns.

Amino Acid Sequence↗
PubMed2001

Epithelial development and differentiation in the mammary gland is not dependent on alpha 3 or alpha 6 integrin subunits.

In the mammary gland, both laminin and integrins have been shown to be required for normal ductal morphogenesis during development in vivo, and for functional differentiation in culture models. Major integrin receptors for laminins in the mammary gland are alpha 3 beta 1, alpha 6 beta 1, and alpha 6 beta 4. However, the specific subunits that contribute to laminin-mediated mammary cell function and development have not been identified. In this study, we use a genetic approach to test the hypothesis that laminin-binding integrins are required for the function of the mammary gland in vivo. Rudiments of embryonic mammary gland were shown to develop in the absence of these integrin subunits. Postnatal development of the mammary gland was studied in integrin null tissue that had been transplanted into the mammary fat pads of syngeneic hosts. In mammary epithelium lacking alpha 6 integrin, the beta 4 subunit was not apparent and hemidesmosome formation was only rudimentary. However, despite this deficiency, normal ductal morphogenesis and branching of the mammary gland occurred and myoepithelial cells were distributed normally with respect to luminal cells. Mammary alveoli devoid of alpha 3 or alpha 6 integrin formed in pregnancy and were histologically and functionally identical to those in wild-type mammary gland. The tissue underwent full morphological differentiation, and the epithelial cells retained the ability to synthesize beta-casein. This work demonstrates that mammary tissue genetically lacking major laminin-binding integrin receptors is still able to develop and function.

Animals↗
PubMed1994

Proteolytic cleavage of the integrin beta 4 subunit.

The integrin beta 4 subunit often undergoes proteolytic cleavage within its long cytoplasmic tail to yield a characteristic protein pattern of 205, 165, and 125 kDa. The results in this study suggest that beta 4 cleavage often occurs during or after cell lysis, where it was readily inhibitable by calcium chelators (EDTA, EGTA) and inhibitors of cysteine proteases (E64c, leupeptin). The cleavage of beta 4 is catalyzed by a calpain-like enzyme because (i) it requires calcium, (ii) it is mimicked by purified milli-calpain, and (iii) it is inhibited by several calpain inhibitors including the calpain-specific inhibitor calpastatin. Within intact cells, cleavage of beta 4 was cell type-specific and observed only when the cells were made permeable to calcium. Substantial cell viability was retained during beta 4 cleavage induced by ionomycin plus calcium, indicating that cleavage within intact cells was not necessarily a consequence of cell death. However, manipulations of cells including suspension, synchronization, and stimulation with serum, phorbol esters, or other agents all failed to induce cleavage, suggesting that if cleavage is physiologically relevant, it is not easily duplicated in vitro. Analysis of multiple cell types showed a wide variation in beta 4 sensitivity to proteolytic cleavage, suggesting that this process might be differentially regulated depending on the cellular environment.

Antigens, Surface↗
PubMed1996

The beta 4 integrin subunit is expressed in mouse fibroblasts and modulated by transforming growth factor-beta 1.

Integrin beta 4 subunit is present in association with alpha 6 chain on both normal and transformed epithelial cells. Recently alpha 6 beta 4 heterodimer was found on the endothelium of medium-sized blood vessels and on immature thymocytes. In this report we show, by Northern blotting, indirect immunofluorescence, immunoprecipitation, and Western blotting, that beta 4 subunit is expressed also on cells of mesenchymal origin such as fibroblasts, myoblasts, and myotubes. Increased expression of alpha 6 beta 4 has been related to the aggressive metastatic phenotype of human and murine carcinomas. The transforming growth factor beta 1 (TGF-beta 1) has been found to modulate the expression of several integrins and intracellular matrix proteins, as well as to stimulate cell invasion and metastatic potential. To evaluate whether alpha 6 beta 4 expression is modulated by TGF-beta 1, we transfected 3T3 fibroblasts with an expression vector carrying the human TGF-beta 1 cDNA driven by the SV40 early promoter. We observed by indirect immunofluorescence a modification in the subcellular distribution of beta 4 subunit, which acquires a perinuclear localization. This finding suggests this integrin subunit correlates with the cytoskeletal reorganization induced by TGF-beta 1.

3T3 Cells↗
PubMed1997

Cleavage of beta 4 integrin by matrilysin.

Overexpression of the matrix metalloproteinase matrilysin and the absence of beta 4 integrin are two features characteristic of human prostate carcinoma. In the following study we demonstrate that the beta 4 integrin, but not the alpha 6 or beta 1 integrin subunits, is cleaved by matrilysin in vitro. A specific fragment of 90 kDa is generated using matrilysin, which is not observed with other proteases. Two putative cleavage sites for matrilysin within the extracellular domain of the beta 4 integrin at residues 107 (isoleucine, prior to the ligand-binding region) and 417 (leucine, prior to cysteine-rich region) are identified by sequence comparisons with known matrilysin substrates. The selective cleavage of the beta 4 integrin by matrilysin may partly explain the loss of beta 4 integrin expression in invasive prostate carcinoma.

Antigens, CD↗
PubMed1997

Expression of integrin receptors on plasma membranes of primary corneal epithelial cells is matrix specific.

Modulation of cell behavior may occur through cell adhesion receptors that bind domains of extracellular matrix molecules and mediate cell-substrate signal transduction. It was hypothesized that while primary corneal epithelial cells seeded onto laminin and fibronectin express and synthesize integrin receptors, they are not detected on the plasma membrane until the appropriate ligand is present. The integrin subunits (alpha-6, beta-4 and beta-1) present on the plasma membrane after adherence to laminin and fibronectin were compared with changes that occurred in mRNA expression and protein synthesis. Prior to seeding, the percentage of cells expressing integrin receptors and matrix proteins on their plasma membrane was determined. Negligible laminin and fibronectin (0-7%) were present on the plasma membrane while the population of epithelial cells expressing beta-4 and beta-1 on the plasma membrane was low (21-23%). After 3 hr of adherence the cell population expressing integrin subunits was substrate dependent. The percentage of cells adherent to LM expressing beta-4 was four-fold greater than cells adherent to FN. After 24 hr the percentage of cells cultured on fibronectin expressing beta-4 increased significantly indicating ligand deposition. The expression and protein synthesis of alpha-6 and beta-4 was evaluated and an increase in the synthesis of alpha-6 and beta-4 was not detected until 18 hr on LM and 21 hr on FN. The present results demonstrate that expression and transport of integrin receptors to the plasma membrane of primary corneal epithelial cells after adhesion is regulated by the presence of specific ligands.

Animals↗
PubMed2002

Cellular and molecular alterations in spinal cord injury patients with pressure ulcers: a preliminary report.

The study was designed to investigate the changes, both numerically and functionally, of the molecules critical to wound healing in spinal cord injury (SCI) patients. Spinal cord injury patients who demonstrated delayed healing of their pressure ulcers were used as study subjects. Age-matched healthy individuals served as controls. Adhesion molecule expression of the peripheral blood leukocytes, including lymphocytes and granulocytes, was measured by flow cytometric analysis. Binding capacity of the lymphocytes was evaluated using human umbilical cord vein endothelial cells (HUVECs) as the binding matrix. Samples from pressure ulcers of the patients were immunostained to define fibronectin, kalinin, beta4 integrin, alpha2beta1, alpha3beta1, alpha5beta1, and CD138 expression. Compared to healthy controls, there was decreased expression of CD11a, CD11b, CD18, CD49b, CD49c, CD49d, CD54, and CD8 in patients' lymphocyte populations and CD11a, CD18, CD49c, CD49d, and CD8 in patients' granulocyte populations. The binding capacity, expressed as percentage binding of the lymphocytes to the HUVEC matrix, was greatly diminished in the patients. There was markedly diminished immunohistochemical staining of fibronectin in pressure ulcers. These findings showed that delayed healing of pressure ulcers in SCI patients can be attributed to reduced adhesion molecule expression, impaired cell-cell interaction, and lack of extracellular matrix structural and functional protein.

Adult↗
PubMed1994

In situ expression of beta 1, beta 3 and beta 4 integrin subunits in non-neoplastic endothelium and vascular tumours.

Endothelial cells play an important role in adhesive interactions between circulating cells and extracellular matrix proteins. In vitro studies have shown that many of these processes are mediated by a superfamily of alpha beta heterodimeric transmembrane glycoproteins called integrins. The distribution patterns of beta 1, beta 3 and beta 4 integrin subunits in endothelial cells (EC) in situ were examined immunohistochemically on serial frozen sections of a wide range of non-neoplastic tissues and of vascular tumours, both benign and malignant. Expression of the beta 1 subunit was a constitutive feature of EC. Among the beta 1-associated alpha subunits, alpha 5 and alpha 6 were broadly distributed in EC, irrespective of vessel size and microenvironment. The alpha 3 subunit displayed intermediate levels of expression with a slight preference for small vessel EC. Presence of alpha 1 was confined to EC of capillaries and venules/small veins. Expression of alpha 2 in EC was inconsistent. With rare exceptions, the alpha 4 chain was absent in EC. The beta 3 and alpha v subunits were expressed in most EC, though not always concomitantly. In contrast to the beta 1 chain, however, these integrin subunits were absent in EC of glomerular capillaries and were expressed variably in sinusoidal EC. The beta 4 chain was evenly present in the great majority of EC, except for those of large vessels. In vascular tumours, the patterns of beta 1 and alpha 1 to alpha 6 subunit expression generally corresponded to those found in their non-neoplastic counterparts. Expression of beta 3, alpha v and beta 4 chains, however, decreased in neoplasia, especially in angiosarcomas. These data show that EC dispose of broad and at the same time differential repertoires of integrin subunits that presumably reflect vessel-type associated functional differences among these cells. In vascular tumours, the orthologous distribution patterns of beta 1 and alpha 1 to alpha 6 chains are conserved in most instances while the amounts of beta 3, alpha v and beta 4 subunits expressed in EC tend to decrease in the course of malignant transformation.

Antibodies, Monoclonal↗
PubMed1995

Differential expression of beta 1, beta 3 and beta 4 integrins in sarcomas of the small, round, blue cell category.

Integrins are a large and complex family of membrane spanning alpha beta heterodimeric cell surface glycoproteins mediating cell/cell and cell/matrix interactions. Small, round, blue cell sarcomas (SRBCS) are a group of poorly differentiated tumours of various and in part uncertain histogenesis displaying similar cytomorphology. Among them are rhabdomyosarcomas (RMS), ganglioneuroblastomas [(G)NB], primitive peripheral neuroectodermal tumours (pPNET) and Ewing's sarcomas (ES). Thirty-two SRBCS were studied immunohistochemically for the distribution of beta 1, beta 3 and beta 4 integrins in situ. We found complex and to some extent differential patterns of beta 1, beta 3 and beta 4 integrin subunit expression in different types of SRBCS: all of the sarcomas studied were consistently beta 1+, beta 4-, alpha 2-. Four of nine RMS were completely negative for all other integrin subunits studied while one RMS was alpha 5+ throughout and three RMS were focally alpha 5+. Three RMS expressed the alpha 6 and alpha v chains. In contrast to RMS, pPNET and ES, all of which were alpha 1-, alpha 3-, (G)NB were alpha 3+ and frequently co-expressed alpha 1. The eight pPNET and seven ES studied showed a similarly restricted integrin profile that was limited to the expression of beta 1 and alpha 5 in nearly all cases. In summary, RMS were beta 1+, alpha 1-, alpha 3- and heterogeneously expressed alpha 5 and alpha 6. (G)NB were generally beta 1+, alpha 1+, alpha 3+, alpha 5-, alpha 6-. pPNET and ES were beta 1+, alpha 1-, alpha 3-, alpha 5+, alpha 6-. The data illustrate a complex expression pattern of various integrins in SRBCS, a differential expression pattern of some of the integrin subunits among different types of SRBCS and almost identical integrin profiles in pPNET and ES.

Ganglioneuroblastoma↗
PubMed2001

Expression profiles of cell-cell and cell-matrix junction proteins in developing human epidermis.

The spatial distribution of a panel of cell junction proteins was studied in developing human epidermis by confocal laser scanning microscopy. The results demonstrated that many of the cell junction proteins were expressed in early two-layered embryonic epidermis, but their subcellular distribution displayed marked changes during development. Specifically, desmosomal proteins, desmoplakin, desmocollin and desmoglein, adherens junction components, E-cadherin, alpha-catenin and vinculin, and an actin-binding protein alpha-actinin were expressed as early as 8 weeks of estimated gestational age (EGA). Type IV collagen and beta1 and beta4 integrins were also present. At this early developmental stage, the epidermis is known to comprise two layers of cells, the basal layer and the peridermal layer. In addition to being present in cell-cell contacts, desmosomal antigens and E-cadherin were unexpectedly localized to the basal aspect of basal cells in samples at 8 weeks. On the other hand, talin, which in adult skin is localized to the dermal-epidermal junction, could not be detected until 12 weeks. These results suggest that the separation of cell membranes to the basal and apicolateral compartments does not occur before the maturation of the basement membrane zone. At 8 weeks EGA, gap junction antigen connexin 43 was expressed in scarce spots in cell-cell contacts of basal cells. In samples of 11-21 weeks EGA, the density of desmosomal and adherens junction markers as well as connexin 43 increased in cell-cell junctions, together with the appearance of the intermediate cell layer and beginning of stratification of the epidermis.

Actinin↗
PubMed2006

The effect of gelatin-chondroitin sulfate-hyaluronic acid skin substitute on wound healing in SCID mice.

Tissue-engineered skin substitutes provided a feasibility to overcome the shortage of skin autograft by culturing keratinocytes and dermal fibroblasts in vitro. In this study, we applied bi-layer gelatin-chondrointin-6-sulfate-hyaluronic acid (gelatin-C6S-HA) biomatrices onto the severe combined immunodeficiency (SCID) mice to evaluate its effect on promoting wound healing. Human foreskin keratinocytes and dermal fibroblasts were cultured with reconstructed skin equivalent (rSE) for 7 days. The rSE was then grafted to the dorsum of SCID mice to evaluate its biocompatibility by histologic and immunohistochemistry analysis. The results showed that human epidermis were well-developed with the expression of differentiated markers and basement membrane-specific proteins at 4 weeks. After implantation, the percentages of skin graft take were satisfactory, while cell-seeded group was better than non-cell-seeded one. The basement membrane proteins including laminin, type IV collagen, type VII collagen, integrin alpha6, and integrin beta4 were all detected at the dermal-epidermal junction, which showed a continuous structure in the 4 weeks after grafting. This bi-layer gelatin-C6S-HA skin substitute not only has positive effect on promoting wound healing, but also has high rate of graft take. This rSE would have the potential to be applied on the extensively and deeply burned patients who suffer from severe skin defect in the near future.

Animals↗
PubMed2006

Expression of laminin 5 by parental and c-Ha-ras-transformed HaCaT keratinocytes in organotypic cultures.

Tumor cells traverse the basement membrane zone and gain access to the underlying mesenchyme to eventually form metastases. Laminin 5 is a major component of the basement membrane and connects keratinocytes at the level of hemidesmosomes to the mesenchyme. Underneath invading tumor cells anti-laminin 5 staining is diminished, and laminin 5 degradation products can stimulate cell migration and epidermal growth factor (EGF) receptor signaling. To investigate laminin 5 expression in parental HaCaT and tumorigenic c-Ha-ras-transformed HaCaT II-4rt keratinocytes, the cells were cultivated under monolayer and organotypic culture conditions. In monolayer cultures, HaCaT and c-Ha-ras-transformed HaCaT II-4rt keratinocytes secreted comparable amounts of laminin 5. After 7 days of organotypic cultures, collagen IV, beta4-integrin, nidogen and laminin 5 were detected along the epithelial-mesenchymal interface of parental HaCaT keratinocytes, while staining for these proteins was patchy or absent in the organotypic cultures with c-Ha-ras-transformed HaCaT II-4rt cells. Immunoblotting analysis confirmed absence of laminin 5 deposition in organotypic cultures of c-Ha-ras-transformed HaCaT II-4rt while the protein was detected in organotypic cultures of HaCaT keratinocytes. Surprisingly, however, the alpha3 and gamma2 laminin chain transcripts were strongly induced in c-Ha-ras-transformed HaCaT II-4rt cells by organotypic culture conditions, indicating that invasive epidermal tumor cells retain high mRNA levels for laminin 5 chains and suggesting an autocrine/paracrine induction of the laminin chain mRNAs. Moreover, as laminin 5 was absent in organotypic cultures of c-Ha-ras-transformed HaCaT II-4rt cells, it suggests immediate degradation of the protein. Degradation products may further contribute to the malignant phenotype by enhancing cellular migration and EGF-receptor activation.

Cell Adhesion Molecules↗
PubMed2006

A new dermal equivalent: the use of dermal fibroblast culture alone without exogenous materials.

BACKGROUND: During the past decade, several kinds of skin equivalents have been developed. However, the dermal equivalents have all contained exogenous materials, which can be difficult to obtain and a source of infections. OBJECTIVES: The aim of this study was to develop a new dermal equivalent by culturing dermal fibroblasts alone without exogenous materials and to evaluate its applicability in vitro and in vivo. METHODS: The postconfulent cultures of dermal fibroblasts in serum containing medium, that was supplemented with epidermal growth factor, insulin, hydrocortisone, transferrin and triiodothyronine for 3 weeks, produced a fibrous sheet that was visible macroscopically. To construct a skin equivalent, epidermal keratinocytes were cultured on the top of the fibrous sheet at the air-liquid interface. To evaluate its fate in vivo, the fibrous sheet was grafted into a nude mouse. RESULTS: Histologically, the fibrous sheet showed dermis-like tissue that consisted of an extracellular matrix around dermal fibroblasts, and revealed collagen fibers by Masson-trichrome staining. The components of dermal matrix such as type I collagen, type III collagen, elastin, fibrillin-1 and fibronectin were diffusely expressed. Some collagen fibrils were found by electron microscopy. In the skin equivalent, a multilayered epidermis with a horny layer was formed. Some differentiation markers (keratin 1 and 10, and involucrin) and the components of basement membrane (beta4 integrin chain, type IV and VII collagens) were expressed in a similar fashion to those in normal skin in vivo. Ultrastructurally, basement membrane zone such as hemidesmosomes, lamina lucida and lamina densa was found, although it was still incomplete. When the fibrous sheet was grafted in vivo, it revealed blood vessels that were derived from the nude mouse, and persisted for 4 weeks. CONCLUSION: These findings demonstrated that a new dermal equivalent, closely resembling a dermis in vivo, could be constructed by culturing dermal fibroblasts alone in a special culture medium. In addition, the dermal equivalent may be useful for experimental and clinical purposes, such as the reconstruction of a skin equivalent in vitro and grafting in vivo.

Animals↗
PubMed2005

Progesterone-induced inhibition of growth and differential regulation of gene expression in PRA- and/or PRB-expressing endometrial cancer cell lines.

OBJECTIVE: Progesterone plays an important role in controlling proliferation and differentiation of the human endometrium. Because there are two progesterone receptor isoforms (PRA and PRB), it was important to generate tools to be able to study the role of these two progesterone receptors separately. METHODS: Using stable transfection techniques, both human progesterone receptor isoforms (hPRA and hPRB) were reintroduced into a hPR-negative subclone of the well-differentiated endometrial cancer cell line Ishikawa. Several Ishikawa subcell lines were constructed, each expressing different levels of hPRA, hPRB, or hPRA and hPRB, respectively. RESULTS: These Ishikawa subcell lines showed a marked progesterone-induced growth inhibition with induction of apoptosis after long-term culture in the presence of hormone. Upon measuring gene regulation, a clear difference in regulation of expression of the selected genes by progesterone treatment was observed between the PRA-, PRB-, or PRA/B-expressing cell lines. Integrin beta4 (ITGB4) was only regulated in PRA-expressing cells; amphiregulin was highly regulated in PRB-expressing cells; insulin-like growth factor binding protein 3 (IGFBP3) was only regulated in PRB- and PRA/B-expressing cells; and metallothionein 1L (MT1L) was highly regulated in PRA/B-expressing cells. Interestingly, based on literature data, these genes can be implicated in induction of apoptosis, but are modulated here in such a way that suggests induction of resistance against apoptosis. CONCLUSION: Reintroduction of PRs into Ishikawa cells rescued progesterone responsiveness in these cells. Furthermore, using these human endometrial cancer subcell lines, clear and distinct functional differences between the PR isoforms were observed.

Apoptosis↗
PubMed2005

PTH-related protein enhances LoVo colon cancer cell proliferation, adhesion, and integrin expression.

Parathyroid hormone-related protein (PTHrP) has been localized in human colon cancer tissue and cell lines. Tumor cell adhesion to extracellular matrix (ECM) proteins plays a major role in the invasion and metastasis of tumor cells, and is mediated via integrin subunits. The LoVo human colon cancer cell line was used as a model system to study the effects of PTHrP on cell proliferation and adhesion to ECM proteins found in normal liver. Clones of LoVo cells engineered to overexpress PTHrP by stable transfection with a PTHrP cDNA showed enhanced cell proliferation vs. control (empty vector-transfected) cells. PTHrP-overexpressing cells also showed significantly higher adhesion to collagen type I, fibronectin, and laminin, and enhanced expression of the [symbol: see text] integrin subunits. These results indicate that PTHrP may play a role in colon cancer invasion and metastasis by increasing cell proliferation and adhesion to the ECM via upregulation of proinvasive integrin expression.

Acid Phosphatase↗
PubMed1997

A structure prediction for the ligand-binding region of the integrin beta subunit: evidence for the presence of a von Willebrand factor A domain.

The integrins are a family of cell surface receptors that mediate biologically important adhesive interactions. Integrin-ligand binding has been extensively studied because of the potential for the development of anti-adhesive therapies, but the molecular basis of this interaction is still poorly understood. A conserved region near the N-terminus of the beta subunit appears to be of particular importance in ligand binding, but to date this domain has not been expressed in isolation. As a prelude to expression and potential structure determination, we have performed a detailed structure prediction for this region. Primary, secondary and tertiary structure analyses indicate that the region folds into a von Willebrand factor A-domain, thereby potentially placing a previously characterised module at the centre of a key functional region.

Algorithms↗
PubMed1997

Immunolocalization of integrins in the normal lung and in pulmonary carcinomas.

Cryosections of normal adult lung (n = 7) and pulmonary epithelial tumors, including squamous (n = 8), adeno (n = 8), bronchioloalveolar (n = 5), and large cell (n = 4) carcinomas (SCC, ACC, BAC, LCC), carcinoids (Cd, n = 7), and neuroendocrine carcinomas (NEC) of variable grades (n = 14) were immunostained by the avidin-biotin peroxidase (ABC) method with monoclonal antibodies to the alpha1-6 and alpha(v) and the beta1-4 integrin subunits. Normal adult alveolar septae showed variably intense immunoreactivity for alpha1,3,6 and beta1, whereas reactions for alpha5 and alpha(v) were weaker and uneven; the remaining integrin subunits were not detected. Bronchial and bronchiolar epithelium showed variably intense staining for alpha2.3,6,v and beta1,4. Reactions were often, though not invariably, basally polarized. SCC, ADC, and LCC showed variably intense reactions for alpha2.3,6,v and beta1,4. BAC were strongly and uniformly stained for alpha1.3 and beta1. In Cd, alpha1,2,3,v and beta1 reactions were noted, whereas in NEC, weak alpha1,3 and beta1 staining was detected with only traces of alpha6 and alpha(v). We conclude that alveolar epithelial cells do not express the hemidesmosome-associated, laminin-binding integrin alpha6beta4 of the bronchial epithelium but rather the alpha1beta1 and alpha3beta1, collagen IV, and laminin receptors, respectively. SCC, ADC, and sampled LCC express an integrin repertory qualitatively similar to that of the bronchial epithelium. Distinct from the latter, the integrin repertory of BAC parallels that of the alveolar epithelium by its strong expression of the multipotential alpha1beta1 and alpha3beta1 integrins. NEC tumors do not display the laminin receptors alpha6beta4 and alpha6beta1 shown by SCC and ADC but express instead alpha1beta1, a collagen IV-laminin receptor rarely found in epithelial neoplasms except for BAC. In NEC tumors, integrins, especially alpha2, decrease with dedifferentiation. Notably distinct from epithelial mesotheliomas, the major fibronectin-binding integrin alpha5beta1 was not found in any type of lung carcinoma.

Adenocarcinoma↗
PubMed1999

Intravenous immunoglobulin therapy for ocular cicatricial pemphigoid: a preliminary study.

OBJECTIVE: To report the effects of intravenous immunoglobulin treatment of ten patients with progressive ocular cicatricial pemphigoid who did not respond to conventional immunomodulatory regimens. DESIGN: Noncomparative, interventional case series. PARTICIPANTS: Ten patients with biopsy-proven progressive cicatricial pemphigoid affecting the eyes who did not respond adequately to other local and systemic immunosuppressive treatment regimens. INTERVENTION: Intravenous infusions of pooled human immunoglobulin, 2 to 3 g/kg body weight/cycle, divided over 3 days, and repeated every 2 to 6 weeks. MAIN OUTCOME MEASURES: Reduction in conjunctival inflammation, prevention of progression of subepithelial conjunctival fibrosis, improvement in ocular symptoms (discomfort, photophobia), improved visual acuity, reduction in extraocular mucosal lesions. RESULTS: Clinical deterioration was arrested and resolution of chronic conjunctivitis was documented in all ten patients. Maximum therapeutic effect was observed and maintained after a minimum of 4 cycles of therapy; three patients required 12 cycles before disease control. The duration of therapy in these ten patients has been 16 to 23 months (mean, 19.3 months) with no treatment-induced side effects. Extraocular mucosal lesion resolution has occurred in all but one patient, Visual acuity has stabilized or improved in all ten patients, and subjective complaints of discomfort and photophobia have decreased in all patients. CONCLUSIONS: Intravenous immunoglobulin immunomodulatory therapy can be a safe and effective therapy for otherwise treatment-resistant ocular cicatricial pemphigoid.

Age of Onset↗