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1.
Br J Cancer ; 86(7): 1169-73, 2002 Apr 08.
Article in English | MEDLINE | ID: mdl-11953867

ABSTRACT

Laminin-1, a heterotrimer of alpha 1, beta 1, and gamma 1 chains specific to basement membrane, promotes cell adhesion and migration, proteinase secretion and metastases of tumour cells. Several active sites on the alpha 1 chain have been found to promote B16-F10 melanoma lung colonisation and here we have determined whether additional tumour promoting sites exist on the beta 1 and gamma 1 chains. Recently, we have identified novel cell adhesive peptides derived from laminin beta 1 and gamma 1 chains by systematic screening of synthetic peptides. Nine beta 1 peptides and seven gamma 1 peptides active for cell adhesion were tested for their effects on experimental pulmonary metastases of B16-F10 mouse melanoma cells in vivo. The most active adhesive peptide derived from the gamma 1 chain globular domain, C-16 (KAFDITYVRLKF), significantly enhanced pulmonary metastases of B16-F10 cells, whereas no other peptides showed enhancement. C-16 also stimulated migration of B16-F10 cells in the Boyden chamber assay in vitro. Furthermore, C-16 significantly induced the production of MMP-9 from B16-F10 cells. These results suggest that this specific laminin gamma 1 chain peptide has a metastasis-promoting activity and might be a new molecular target of anti-cancer treatment.


Subject(s)
Cell Movement/drug effects , Laminin/pharmacology , Lung Neoplasms/secondary , Melanoma/pathology , Neoplasm Metastasis/physiopathology , Peptide Fragments/pharmacology , Animals , Cell Adhesion , Disease Models, Animal , Lung Neoplasms/veterinary , Matrix Metalloproteinase 9/metabolism , Melanoma/veterinary , Mice , Tumor Cells, Cultured
2.
Cancer Lett ; 167(2): 205-13, 2001 Jun 26.
Article in English | MEDLINE | ID: mdl-11369142

ABSTRACT

Squamous cell carcinoma (SCC) antigen has been used for the management of SCC arising in various cites including head and neck region. However, the true mechanism of the elevation of this protein in the serum of patients with SCC is still unknown. SCC antigen belongs to the superfamily of serine protease inhibitors. Recently, molecular studies show that serum SCC antigen is transcribed by two nearly identical genes (SCCA1 and SCCA2), and is mainly produced by SCCA1. The objective of this study is to clarify the mechanism of the elevation of SCC antigen in oral tongue SCC patients and to identify cells histologically, which are responsible for serum SCC antigen production. In this study, we examined SCCA1 expression in a series of four head and neck SCC (HNSCC) cell lines, and found that all expressed equal to low SCCA1 protein as compared with the normal human oral keratinocyte. Using the double immunohistochemical technique to examine the expression pattern of SCCA1 in 86 cases of oral tongue squamous cell carcinoma, SCCA1 immunostaining was observed in the cytoplasm of cancer cells and T-lymphocytes peripheral to cancer cells. We also compared the clinicopathological features including serum SCC antigen level of the oral tongue SCC cases with the immunohistochemical SCCA1 expression pattern, and found that elevated serum SCC antigen level was significantly correlated with SCCA1 expression not in cancer cells, but in T-lymphocytes peripheral to cancer cells. These results suggest that T-lymphocytes peripheral to cancer cells may be responsible for serum SCC antigen production in HNSCC patients.


Subject(s)
Antigens, Neoplasm/biosynthesis , Antigens, Neoplasm/blood , Carcinoma, Squamous Cell/blood , Serpins , T-Lymphocytes/metabolism , Tongue Neoplasms/blood , Adult , Aged , Aged, 80 and over , Blotting, Western , Carcinoma, Squamous Cell/mortality , Female , Humans , Immunohistochemistry , Lymph Nodes/metabolism , Male , Middle Aged , Survival Rate , Tongue Neoplasms/mortality , Tumor Cells, Cultured
3.
Head Neck ; 23(11): 962-6, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11754500

ABSTRACT

BACKGROUND: A relatively high failure rate in the therapy of patients with early oral tongue squamous cell carcinomas (SCCs) is evidenced by untreated clinically negative neck lymph node metastasis. It is important to predict the malignant potential of oral tongue SCC in stage I and II patients, because the development of lymph node metastasis directly affects the prognosis of the patients. METHODS: We evaluated maspin expression immunohistochemically in patients with stage I and II oral tongue SCCs and determined whether the expression level may be a useful factor in predicting metastatic potential and prognosis of these SCCs. RESULTS: Clinical follow-up data showed a longer disease-free interval and overall survival periods for tumors immunohistochemically positive for maspin than for tumors negative for maspin, with the difference in disease-free interval being statistically significant (p =.01). The absence of maspin expression was found more frequently in cases of subsequent cervical lymph node metastasis than in cases without metastasis (p =.03). CONCLUSIONS: Decreased maspin expression may be a significant factor associated with the metastatic potential of stage I and II oral tongue SCCs.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Proteins/metabolism , Serine Proteinase Inhibitors/metabolism , Serpins/metabolism , Tongue Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Brachytherapy , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/secondary , Disease-Free Survival , Female , Genes, Tumor Suppressor , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Tongue Neoplasms/drug therapy , Tongue Neoplasms/mortality , Tongue Neoplasms/pathology , Tongue Neoplasms/radiotherapy
4.
Head Neck ; 22(7): 662-5, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11002320

ABSTRACT

BACKGROUND: Late nodal metastases is a critical factor that worsens the prognosis of T1/T2N0 tongue cancer treated by interstitial brachytherapy. If we could better predict the patients at high risk for late nodal metastases developing before treatment, more appropriate choices of treatment could be selected. In recent studies of colon cancer, prostate cancer, and laryngeal cancer, CD44H has been postulated to be a metastasis suppressor. METHODS: On the basis of this phenomenon, we immunohistochemically evaluated the expression of CD44H in 38 cases of primary T1/T2N0 tongue cancer treated by interstitial brachytherapy. Formalin-fixed, paraffin-embedded biopsy specimens obtained before treatment were examined. RESULTS: The group that had late nodal metastases revealed a significantly lower (p =.0035) CD44H expression. CONCLUSIONS: A decreased CD44H expression may therefore be useful as a new predictor of late nodal metastases in patients with T1/T2N0 tongue carcinoma. For patients with a decreased CD44H expression, a partial glossectomy and an elective neck dissection may therefore be an appropriate treatment modality.


Subject(s)
Brachytherapy , Carcinoma, Squamous Cell/metabolism , Hyaluronan Receptors/metabolism , Tongue Neoplasms/metabolism , Adult , Aged , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/secondary , Female , Humans , Immunohistochemistry , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Prognosis , Retrospective Studies , Survival Analysis , Tongue Neoplasms/pathology , Tongue Neoplasms/radiotherapy
5.
J Neurosci Res ; 61(3): 302-12, 2000 Aug 01.
Article in English | MEDLINE | ID: mdl-10900077

ABSTRACT

The basement membrane protein laminin-1 is a potent stimulator of neurite outgrowth for a variety of neuronal cell types. Previous studies have identified neurite outgrowth activity in several distinct regions of the laminin-1 molecule. In this study, 545 overlapping 12- to 14-mer synthetic peptides, corresponding to most of the amino acid sequence of the alpha1, beta1, and gamma1 chains of laminin-1, were screened for cell attachment and neurite outgrowth activity using primary cultures of mouse cerebellar granule neurons and two neuronal cell lines. We identified 48 peptides derived from novel regions of the laminin-1 molecule that were positive for neural cell adhesion activity. Only the cerebellar cells were found to have true neurite outgrowth activity with certain of the peptides, whereas some peptides induced short spike-like process with the cell lines. Although 23 of these peptides were active on all 3 cell types screened, 25 others showed cell-type specificity in their activity. These studies show that (1) there are multiple and distinct sites on laminin-1 for cell adhesion and neurite-like outgrowth and (2) that there are neural cell-type-specific active domains. The multiple active sites found explains, in part, the potent activity of laminin-1 on neurite outgrowth.


Subject(s)
Laminin/metabolism , Neurons/cytology , Amino Acid Sequence , Animals , Cell Adhesion , Cell Line , Laminin/chemistry , Laminin/pharmacology , Neurites/physiology , Neurons/physiology , Neurons/ultrastructure , PC12 Cells , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , Rats
6.
Arch Biochem Biophys ; 378(2): 311-20, 2000 Jun 15.
Article in English | MEDLINE | ID: mdl-10860548

ABSTRACT

Laminin-1, a major component of the basement membrane, consists of three different chains, alpha1, beta1, and gamma1. We sought to identify cell adhesive sequences from the mouse laminin beta1 chain by testing HT-1080 fibrosarcoma and B16-F10 melanoma cells for binding to 187 overlapping synthetic peptides which covered the entire chain. Fourteen peptides showed cell adhesive activities with either peptide-conjugated Sepharose beads or peptide-coated plates or both. Additional cells, including neuronal, endothelial, and salivary gland cells, showed biological responses in a cell type-specific manner. B-7, B-133, and B-160 showed the most potent cell attachment. Cell binding on three peptides (B-34, B-133, and B-160) was inhibited by EDTA. Cell adhesion to 11 of the 12 active peptides was inhibited to varying degrees by heparin. Of the 17 active peptides identified in the laminin beta1 chain in this and other studies, 8 are clustered on the amino terminal globular domain, suggesting a possible important role in cell binding for this domain that may be multifunctional. These data demonstrate that the laminin beta1 chain has multiple active sites for cell adhesion, some of which are cell-type specific.


Subject(s)
Cell Adhesion/physiology , Laminin/chemistry , Laminin/metabolism , Amino Acid Sequence , Animals , Cell Adhesion/drug effects , Cell Line , Cells, Cultured , Dose-Response Relationship, Drug , Edetic Acid/metabolism , Endothelium, Vascular/metabolism , Fibrinolytic Agents/pharmacology , Heparin/pharmacology , Humans , Mice , Models, Biological , Molecular Sequence Data , Peptides/metabolism , Protein Binding , Rats , Sepharose/metabolism , Sequence Homology, Amino Acid , Tumor Cells, Cultured
7.
Exp Cell Res ; 249(2): 386-95, 1999 Jun 15.
Article in English | MEDLINE | ID: mdl-10366438

ABSTRACT

Laminin-1, a major basement membrane matrix glycoprotein, enhances adhesion, migration, and metastasis of tumor cells. We have screened 208 overlapping synthetic peptides covering the short and long arms of mouse laminin alpha1 chain for their adhesion activity with B16-F10 mouse melanoma cells. Cell adhesion activity was determined using various amounts of peptides coated on plastic dishes and by measuring cell adhesion on peptide-conjugated Sepharose beads. Nineteen peptides showed B16-F10 cell adhesion activity. Three peptides, designated A-13, -24, and -208, showed the strongest attachment activity in the plate assay, whereas 4 peptides, A-13, -51, -99, and -112, demonstrated the strongest cell adhesion when conjugated to beads. The 19 peptides were tested in vivo for their effect on experimental pulmonary metastasis by B16-F10 cells. Four peptides, A-13, -51, -64, and -119, significantly enhanced metastasis, with A-13 showing the strongest dramatic enhancement. The four metastasis-promoting peptides also stimulated migration of B16-F10 cells in the Boyden chamber assay in vitro with A-13 being the most potent stimulator. In addition, the 4 peptides inhibited laminin-induced cell attachment and migration, which indicates that these four sequences are possible functional B16-F10 cell binding sites in laminin-1. All the four sequences are located on the globular domains of the short arm. Other peptides, including strong adhesion-active peptides, A-24, -99, -112, and a scrambled A-13 peptide, did not stimulate either migration or metastasis. Thus, laminin-1 has multiple active sites in the globular domains of the short arm which promote migration and metastasis of B16-F10 cells.


Subject(s)
Laminin/physiology , Lung Neoplasms/secondary , Melanoma, Experimental/secondary , Peptides/physiology , Animals , Cell Adhesion , Cell Movement , Injections, Intravenous , Laminin/chemistry , Lung Neoplasms/pathology , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Microspheres , Neoplasm Transplantation , Peptides/metabolism
8.
Eur Arch Otorhinolaryngol ; 256 Suppl 1: S60-3, 1999.
Article in English | MEDLINE | ID: mdl-10337530

ABSTRACT

The overall survival rate (OSR) of 36 patients with nasopharyngeal carcinomas (NPC) treated at Kyushu University hospital between 1983 to 1992 was analyzed. As primary treatment, 16 patients received a combination therapy of 5-fluorouracil, vitamin A, and radiation (FAR therapy); two patients received radiotherapy only; 18 patients received FAR therapy plus adjunctive systemic chemotherapy consisting of cisplatin and peplomycin. The radiation dose to the nasopharynx was 6000 to 7050 cGy while that to the neck was 4000-6000 cGy. The 5-year OSR of all the patients was 49%. Histological type (moderately differentiated squamous cell carcinoma) and patient age (> or = 55) were found to be significant prognostic factors for a worse OSR. Although survival decreased with increasing T stage, no significant difference was observed. The 5-year OSR of the patients treated with FAR therapy was 53% and was 51% with FAR therapy plus chemotherapy. Compared to FAR therapy alone, adjunctive chemotherapy did not increase OSR of the patients with NPC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/mortality , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/mortality , Neoplasm Staging , Peplomycin/administration & dosage , Retrospective Studies , Survival Rate , Vitamin A/administration & dosage
9.
Respirology ; 4(1): 53-61, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10339731

ABSTRACT

The aim of this study was to confirm the validity and reliability of a new diary-type quality of life (QOL) self-rating questionnaire tailored for use by Japanese inpatients with lung cancer receiving chemotherapy. Two kinds of summary statistics were tested in QOL analysis. The questionnaire has a four-scale structure; physical, psychological, daily activity and global scales. Fifty-three patients were enrolled to test the reliability and validity. Summary statistics were assessed using indices of the area under the curve (AUC) and the maximum fluctuations of QOL scores (Dif max) in patients receiving cisplatin or carboplatin. The questionnaire had satisfactory reliability and validity. The physical, psychological and global scales scores changed to the worst levels after treatment, continuing for 1 week in the cisplatin group, whereas those of the carboplatin group began to worsen from day 3, but returned to prechemotherapy levels by day 9. The cisplatin group showed significant decrease of QOL compared with the carboplatin group in the AUC of psychological and two global scales, in the Dif max of psychological and linear analogue global scales. These results suggested that this questionnaire reflects differences in the influence of chemotherapy, and that AUC and Dif max may be useful indices for the analysis of QOL as measures to assess multidimensional QOL.


Subject(s)
Antineoplastic Agents/therapeutic use , Lung Neoplasms/psychology , Medical Records , Quality of Life , Surveys and Questionnaires , Adult , Aged , Carboplatin/therapeutic use , Cisplatin/therapeutic use , Drug Therapy/psychology , Female , Humans , Japan , Lung Neoplasms/drug therapy , Male , Middle Aged , Reproducibility of Results
10.
Circ Res ; 84(6): 688-94, 1999 Apr 02.
Article in English | MEDLINE | ID: mdl-10189356

ABSTRACT

The laminins belong to a family of trimeric basement membrane glycoproteins with multiple domains, structures, and functions. Endothelial cells bind laminin-1 and form capillary-like structures when plated on a laminin-1-rich basement membrane matrix, Matrigel. Laminin-1 is composed of 3 chains, alpha1, beta1, and gamma1. Because laminin-1 is known to contain multiple biologically active sites, we have screened 156 synthetic overlapping peptides spanning the entire laminin gamma1 chain for potential angiogenic sequences. Only 7 of these peptides, designated as C16, C25, C30, C38, C64, C75, and C102, disrupted the formation of capillary-like structures by human umbilical vein endothelial cells on Matrigel. Dose-response experiments in the presence of 50 to 200 microg/mL showed that tube formation was prevented by most peptides at 150 and 200 microg/mL, except for C16, which showed strong activity at all concentrations. Active peptides promoted vessel sprouting from aorta rings and angiogenesis in the chick chorioallantoic membrane assay. In addition, the active peptides also promoted endothelial cell adhesion to dishes coated with 0.1 microg of peptide and inhibited attachment to laminin-1 but not to plastic or fibronectin. Four of the active peptides, C25, C38, C75, and C102, may have cell-type specificity with endothelial cells, since they did not promote PC12 neurite outgrowth or adhesion of B16-F10 melanoma and human submandibular gland cells. These results suggest that specific laminin gamma1-chain peptides have angiogenic activity with potential therapeutic applications.


Subject(s)
Endothelium, Vascular/metabolism , Laminin/metabolism , Allantois/blood supply , Amino Acid Sequence , Animals , Aorta/cytology , Aorta/drug effects , Binding Sites/drug effects , Cell Adhesion/drug effects , Cell Division/drug effects , Chick Embryo , Chorion/blood supply , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Humans , Infant, Newborn , Laminin/antagonists & inhibitors , Laminin/chemistry , Molecular Sequence Data , Neovascularization, Physiologic/drug effects , Peptides/physiology , Rats , Rats, Sprague-Dawley
11.
FASEB J ; 13(1): 53-62, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9872929

ABSTRACT

Laminin-1 is a basement membrane glycoprotein that promotes several biological activities including cell attachment, tumor metastasis, and angiogenesis. Angiogenesis plays an important role in tissue formation, reproduction, wound healing, and several pathological conditions. In this study, we screened 405 synthetic peptides from the alpha1 and beta1 chains to identify potential sites on laminin-1 active with endothelial cells. Peptides were initially screened by testing both endothelial cell adhesion to peptide-coated wells and tube formation on Matrigel in the presence of soluble peptide. Twenty active peptides were identified in these screens. A secondary screen using the rat aortic ring sprouting assay identified 13 of the 20 peptides that stimulated endothelial sprouting. Several of these active peptides were also found to stimulate human umbilical vein endothelial cell migration in Boyden chamber assays. Differences in the amount of peptide needed for the response and in the resultant morphologies/responses were observed between the peptides in all of the assays. Our results suggest that several active domains on laminin-1 may play important roles in stimulating different steps in angiogenesis.


Subject(s)
Cell Adhesion , Endothelium, Vascular/cytology , Laminin/physiology , Neovascularization, Physiologic/physiology , Amino Acid Sequence , Animals , Aorta/physiology , Cell Movement , Cells, Cultured , Humans , Laminin/chemical synthesis , Molecular Sequence Data , Peptides/chemical synthesis , Peptides/metabolism , Rats , Structure-Activity Relationship
12.
J Biol Chem ; 273(49): 32491-9, 1998 Dec 04.
Article in English | MEDLINE | ID: mdl-9829982

ABSTRACT

Laminin-1, a multifunctional glycoprotein of the basement membrane, consists of three different subunits, alpha1, beta1, and gamma1 chains. Previously, we used synthetic peptides to screen for biologically active sequences in the laminin alpha1 chain C-terminal globular domain (G domain) and identified several cell binding sequences (Nomizu, M., Kim, W. H., Yamamura, K., Utani, A., Song, S. Y., Otaka, A., Roller, P. P., Kleinman, H. K., and Yamada, Y. (1995) J. Biol. Chem. 270, 20583-20590). Here, we identify new cell binding sequences on the remainder of the laminin alpha1 chain by systematic peptide screening, using 208 overlapping synthetic peptides encompassing the central and N-terminal portions of the alpha1 chain. HT-1080 cell attachment activity to the peptides was evaluated using peptide-coated plastic substrates and peptide-conjugated Sepharose beads. Twenty five peptides showed cell attachment activities on either the peptide-coated plastic substrates and/or the peptide-conjugated Sepharose beads. A-13 (RQVFQVAYIIIKA) showed strongest cell attachment activity in both the assays. Cell attachment to 14 of the peptides was inhibited by heparin. EDTA and integrin antibodies inhibited cell adhesion to two of the peptides, A-13 and A-25, suggesting that these sites likely bind to integrins. These peptides inhibited cell attachment to laminin-1 but not to collagen I, suggesting these active sites are available on the intact molecule. Most of active sequences were localized on globular domains suggesting that these structures play a critical role in binding to cell-surface receptors.


Subject(s)
Laminin/metabolism , Amino Acid Sequence , Animals , Antibodies/immunology , Cell Adhesion , Edetic Acid/immunology , Humans , Integrins/immunology , Laminin/chemistry , Mice , Molecular Sequence Data , Peptide Fragments/metabolism , Protein Binding , Tumor Cells, Cultured
13.
Int J Cancer ; 77(4): 632-9, 1998 Aug 12.
Article in English | MEDLINE | ID: mdl-9679769

ABSTRACT

We earlier screened overlapping synthetic peptides from the globular domain of the laminin alpha1 chain to identify active sites for cell attachment. We report here that one of the active cell-adhesion peptides, AG-73 (Arg-Lys-Arg-Leu-Gln-Val-Gln-Leu-Ser-Ile-Arg-Thr; RKRLQVQLSIRT) causes B16F10 murine melanoma cells to metastasize to the liver, a site not normally colonized by these cells. Increases in liver metastases and in lung colonization are observed in immune-deficient beige/nude/xid and in C57Bl/6 mice with this peptide. This metastatic activity was observed with i.v. and with i.p. peptide injections, regardless of tumor cell or of peptide-injection times. In vitro, the AG-73 peptide enhances tumor cell adhesion, migration, invasion, and gelatinase production, and blocks laminin-1-mediated cell migration. AG-73 was found to significantly inhibit cell adhesion to a proteolytic laminin-1 fragment, E3, containing the AG-73 sequence. Cell attachment to AG-73, the E3 fragment, and laminin-1 involved cation-dependent receptors. We report that a laminin peptide has the novel and unexpected activity of causing B16F10 melanoma cells, a lung selected cell line, to metastasize to the liver. The minimal active sequence of AG-73, LQVQLSIR, could be one of the most important biologically active sites of laminin-1, especially in promotion of the malignant phenotype. Activation of the malignant phenotype by this peptide provides a significant new model for understanding metastatic mechanisms.


Subject(s)
Laminin/pharmacology , Melanoma, Experimental/secondary , Peptide Fragments/pharmacology , Animals , Cell Adhesion/drug effects , Chemotaxis/drug effects , Gelatinases/metabolism , Laminin/physiology , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Melanoma, Experimental/enzymology , Mice , Mice, Inbred C57BL , Mice, Nude , Neoplasm Invasiveness , Neoplasm Proteins/metabolism , Peptide Fragments/physiology
14.
Nihon Kyobu Shikkan Gakkai Zasshi ; 35(8): 910-4, 1997 Aug.
Article in Japanese | MEDLINE | ID: mdl-9366169

ABSTRACT

A 58-year-old woman because of coughing and an abnormality on a chest renggenogram was referred to our hospital. A chest X-ray film and a computed tomogram revealed atelectasis of the right lower lobe and a round tumor in the left lower lobe. Fiberoptic bronchoscopy revealed an endobronchial polypoid tumor in the intermediate bronchus, which completely obstructed the orifice of the right lower-lobe bronchus. Microscopical examination revealed B-cell diffuse, large, non-Hodgkin's lymphoma. No extrapulmonary lesion was found, and therefore primary pulmonary non-Hodgkin's lymphoma was diagnosed. Chemotherapy resulted in rapid and complete regression of the tumor, which was confirmed endoscopically and histologically. The patient was still in complete remission 8 months after the end of chemotherapy. There have been no additional interventions.


Subject(s)
Bronchial Neoplasms/pathology , Lung Neoplasms/pathology , Lymphoma, B-Cell/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Polyps/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bronchial Neoplasms/drug therapy , Female , Humans , Lung Neoplasms/drug therapy , Lymphoma, B-Cell/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Middle Aged , Polyps/drug therapy , Remission Induction
15.
No Shinkei Geka ; 25(7): 635-9, 1997 Jul.
Article in Japanese | MEDLINE | ID: mdl-9218258

ABSTRACT

We report a case of a penetrating cranio-facial injury due to a nail-gun accident. An 18-year-old worker was admitted to our hospital as an emergency patient. He was working using a nail-gun when a nail ricocheted off a wall and pierced the right side of his face. Skull X-rays and a CT scan showed that a 9 cm nail had pierced his right frontal lobe through the right maxillary bone via the orbital space. The patient was alert without any neurologically abnormal findings. A small stab wound was recognized on his face. The nail was removed six hours after the injury through a sublabial approach and a fronto-temporal craniotomy. The nail was very tightly fixed in the maxillary bone and skull base bones, and a screw driver normally used in orthopedic surgery proved to be very useful for removing the nail. The patient returned home 14 days later without any neurological deficits. The technical problems associated with such a nail-gun injury in the face and skull are also discussed.


Subject(s)
Brain Injuries/surgery , Construction Materials , Facial Injuries/surgery , Foreign Bodies/surgery , Adolescent , Humans , Male , Orbit/injuries , Orthopedic Equipment
16.
J Biol Chem ; 272(51): 32198-205, 1997 Dec 19.
Article in English | MEDLINE | ID: mdl-9405421

ABSTRACT

Laminin-1, a major component of basement membranes, consists of three different chains designated alpha1, beta1, and gamma1 and has diverse biological functions. We have identified cell binding sites on the mouse laminin gamma1 chain, using systematic screening of 165 overlapping synthetic peptides covering the entire chain. We identified 12 cell binding sequences using HT-1080 human fibrosarcoma and B16-F10 mouse melanoma cells in two independent assays employing peptide-conjugated Sepharose beads and peptide-coated dishes. Four peptides (C-16, C-28, C-64, and C-68) located on the globular domains of the gamma1 chain were the most active and showed dose-dependent cell attachment. Cell attachment to C-68 was inhibited by EDTA and by anti-alpha2beta1 integrin antibodies. Cell attachment to C-16 and C-64 was partially inhibited by EDTA but was not inhibited by anti-integrin antibodies. EDTA and anti-integrin antibodies did not affect cell attachment to C-28. The four peptides were tested in adhesion and differentiation assays with endothelial, neuronal, and human salivary gland cells. C-16 was the most active for all of the cells, whereas the other three peptides showed cell type specificity in their activities. The active core sequences of C-16, C-28, C-64, and C-68 are YVRL, IRVTLN, TTVKYIFR, and SIKIRGTY, respectively. These sequences are highly conserved among the different species and in the laminin gamma2 chain. These results suggest that the specific sequences on the laminin gamma1 chain are biologically active and interact with distinct cell surface receptors.


Subject(s)
Laminin/metabolism , Amino Acid Sequence , Animals , Binding Sites , Cell Adhesion/drug effects , Cell Adhesion/immunology , Cell Line , Edetic Acid/pharmacology , Humans , Integrins/chemistry , Integrins/immunology , Integrins/metabolism , Laminin/chemistry , Mice , Molecular Sequence Data , Receptors, Cell Surface/chemistry , Receptors, Cell Surface/metabolism , Tumor Cells, Cultured
17.
Nihon Kyobu Shikkan Gakkai Zasshi ; 35(10): 1093-8, 1997 Oct.
Article in Japanese | MEDLINE | ID: mdl-9465621

ABSTRACT

A 51-year-old woman was admitted to our hospital with exertional dyspnea, swelling and stiffness in her fingers. Raynaud's phenomenon and mammary and axillary lymphadenopathy. She had received silicone augmentation mammoplasty 30 years ago, and had since noticed bilateral mammary and axillary lymphadenopathy that was stable in size. In the 2 years before admittance she had become aware of an exacerbation of the lymphadenopathy had begun to experience and exertional dyspnea several months before admission suggesting a connective tissue disease. Physical examination revealed symmetrical weakness of the proximal limb muscles and fine crackles in the base of both lungs. Elevated myogenic enzymes, inflammatory reactions, and positive anti-SSA antibody were noted. Based upon these findings, muscle and lip biopsy results, myogenic EMG, and an apple tree appearance on sialography, a differential diagnosis of polymypositis or sjögren's syndrome was made. Axillary lymph node biopsy findings were consistent with silicone lymphadenitis. In addition, chest roentgenogram and HRCT (which revealed decreased lung volumes and interstitial opacities with no honeycombing, present predominatly in the subpleural space), pulmonary function tests (decreased VC and DLco), bronchoalveolar lavage (elevated total cell count and neutrophil and eosinophil fractions), and transbronchial lung biopsy specimens (unevently distributed alveolitis with fibrosis) indicated concurrent interstitial pneumonia. The clinical correlation between exacerbation of silicone lymphadenopathy and the development of connective tissue disease with accompanying interstitial pneumonia strongly suggested human adjuvant disease (HAD) as the pathogenesis. To our knowledge, interstitial pneumonia associated with HAD is rare.


Subject(s)
Breast Implants/adverse effects , Connective Tissue Diseases/etiology , Lung Diseases, Interstitial/etiology , Mammaplasty/adverse effects , Silicones/adverse effects , Female , Humans , Middle Aged
18.
FEBS Lett ; 396(1): 37-42, 1996 Oct 28.
Article in English | MEDLINE | ID: mdl-8906862

ABSTRACT

The laminin alpha1 chain carboxyl-terminal globular domain (G domain) contains multiple biological activities. Recently, we identified five cell binding sequences from the G domain by screening with overlapping 12-mer peptides encompassing the entire domain. The structures of these five sequences in the alpha1 chain are conserved in the corresponding regions of the different laminin alpha chains. Here we characterize the adhesion activities of the corresponding peptide segments from both the mouse laminin alpha2 chain and Drosophila laminin alpha chain using peptide-coated plastic plates and peptide-conjugated Sepharose beads. Using several cell lines, the laminin alpha2 chain peptides showed cell attachment and/or spreading activities with cell type specificities. Cell spreading on MG-10 was inhibited by integrin antibodies. Four of the Drosophila laminin peptides showed cell attachment activities. These results suggest that biologically active regions in the G domain are conserved in the laminin alpha1 and alpha2 chains, and that these regions in laminin play an important role in cell surface receptor interactions.


Subject(s)
Drosophila/chemistry , Laminin/chemistry , Laminin/metabolism , Peptide Fragments/metabolism , Peptide Fragments/pharmacology , Amino Acid Sequence , Animals , Binding Sites , Cell Adhesion/drug effects , Cell Adhesion/physiology , Cells, Cultured , Conserved Sequence , Dose-Response Relationship, Drug , Fibrosarcoma/metabolism , Fibrosarcoma/pathology , Humans , Melanoma/metabolism , Melanoma/pathology , Mice , Models, Molecular , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Peptide Fragments/chemical synthesis , Rats , Sepharose , Tumor Cells, Cultured
19.
Cancer ; 78(3): 390-5, 1996 Aug 01.
Article in English | MEDLINE | ID: mdl-8697381

ABSTRACT

BACKGROUND: Hypopharyngeal squamous cell carcinomas (HPCS) are associated with an extremely poor prognosis. Generally, conventional clinicopathologic factors have only limited value as prognostic factors for this malignancy. It is therefore clinically important to identify new prognostic factors that accurately reflect the biologic aggressiveness of this malignancy. The amplification and overexpression of the cyclin D1 protooncogene have been reported in a variety of malignancies, and are thought to be related to tumor progression. Based on this phenomenon, the authors immunohistochemically evaluated overexpression of the cyclin D1 gene in 42 cases of primary HPCS. In addition, the immunohistochemical staining of the proliferation marker MIB-1 (Ki-67 antibody) was also performed. METHODS: Formalin fixed, paraffin embedded biopsy specimens obtained prior to treatment were examined. Cyclin D1 and Ki-67 were detected using monoclonal antibodies by means of the streptavidin-biotin method. The relationship between cyclin D1 overexpression and the stage, histologic grade, presence of lymph node metastases, proliferation index, and survival was then statistically analyzed. The correlation between the proliferation index, other clinicopathologic factors, and survival was also evaluated. RESULTS: Twenty-three (54.8%) HPCS specimens showed a 20% or greater immunoreactivity for cyclin D1. Cyclin D1 overexpression was related to cervical lymph node metastases (P = 0.037) but not to clinical stage, histologic grade, or the proliferation index. Cyclin D1 negative tumors were associated with a significantly better prognosis (P = 0.023), particularly in patients who underwent multimodality treatment. Finally, the MIB-1 labeling index showed no correlation with either the clinicopathologic parameters or overall survival. CONCLUSIONS: Based on these findings, cyclin D1 immunohistochemical staining is considered to be useful, not only as a prognostic factor for HPCS, but also as a means of determining the optimum treatment for each individual patient. Conversely, the MIB-1 labeling index appears to have no clinical significance in HPCS.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , Cyclins/analysis , Hypopharyngeal Neoplasms/pathology , Oncogene Proteins/analysis , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/analysis , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/mortality , Cyclin D1 , Female , Humans , Hypopharyngeal Neoplasms/chemistry , Hypopharyngeal Neoplasms/mortality , Immunohistochemistry , Ki-67 Antigen , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Proteins/analysis , Nuclear Proteins/analysis , Prognosis , Survival Rate
20.
Kyobu Geka ; 49(2): 122-5, 1996 Feb.
Article in Japanese | MEDLINE | ID: mdl-8691679

ABSTRACT

Two cases of bronchogenic carcinoma undergone left upper lobectomy (R 3) with bronchoplasty and sleeve pulmonary arterial resection via mid-sternotomy were reported. Both cases were squamous cell carcinoma originated in the orifice of the left upper lobe. Case 1 was stage IIIB (T2N3M0) bronchogenic carcinoma, its postoperative course was uneventful and died of distant lymphatic metastasis thirty-three months after operation. Case 2 was stage II (T2N1M0) bronchogenic carcinoma and its postoperative management was laborious because of hard expectoration of the sputum but is doing well fifteen months after operation. In order to preserve adequate pulmonary function and to maintain reasonable quality of life (QOL) for the patients with impaired pulmonary function, this angioplastic procedure seems to be acceptable. It is still under discussion to perform this procedure for the patients who would be able to withstand undergoing pneumonectomy, therefore we adopt this method only for every patient for whom it is difficult to maintain desirable QOL after pneumonectomy. Namely, for the patient whose predicted one second forced expiratory volume (FEV1.0) after pneumonectomy is less than 900 ml/m2, we'll be likely to try this angioplastic procedure at first.


Subject(s)
Carcinoma, Bronchogenic/surgery , Carcinoma, Squamous Cell/surgery , Lung Neoplasms/surgery , Pulmonary Artery/surgery , Aged , Carcinoma, Bronchogenic/physiopathology , Carcinoma, Squamous Cell/physiopathology , Humans , Lung Neoplasms/physiopathology , Male , Middle Aged , Pneumonectomy , Quality of Life
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