OBJECTIVETo describe the clinicopathologic features and immunophenotypes of carcinoid tumorlets in the lung with bronchiectasis, and to study the morphogenesis of these tiny tumors.

METHODSThe histopathologic characteristics of 3 bronchiectasis cases with carcinoid tumorlets, 11 bronchiectasis and 2 normal lungs were studied. Specific markers of the tiny tumors and the number of neuroendocrine cells (NECs) in the airway mucosa were immunohistochemically detected by EnVision method.

RESULTSThe tumorlets in the lungs presented as multi-focal nodules and most were displayed only under microscopy. These cells were arranged in clusters and foci of fascicles which were situated in the surrounding bronchial wall and bronchioles adjacent to bronchiectatic lesion, or in the scar tissues. The tiny tumors were consisted of short fusiform cells and small ovoid cells. Their nuclei were circular, oval or long fusiform and the cells were strongly argyrophilic on Grimelius staining. Intensive positive immunostaining for calcitonin, chromogranin A, NSE and gastrin were detected. Weak positive for CK, EMA, S-100 and focal positive for HC, ACTH, 5-HT were also observed. Proliferative NECs in airway mucosa adjacent to the tiny tumors increased significantly in number, compared with those in the airway mucosa of bronchiectasis without tumorlets and normal lungs (P < 0.001, respectively).

CONCLUSIONSThe clinicopathologic features and immunophenotypes of carcinoid tumorlets resemble carcinoid tumors. They are the early stage of carcinoid development. Their development may be related to the chronic pulmonary damage resulting in hypoxia and stimulating the proliferation of NECs. These pulmonary carcinoid tumorlets can be used as a model to study the tumorigenesis of carcinoid carcinoma of the lung.

Adult ; Aged ; Bronchiectasis ; pathology ; Carcinoid Tumor ; chemistry ; pathology ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms ; chemistry ; pathology ; Middle Aged ; Morphogenesis ; Neurosecretory Systems ; pathology

OBJECTIVETo study the clinicopathological and immunohistochemical features, histogenesis and prognosis of pleuropulmonary blastoma (PPB) in children.

METHODSPPB specimens from 16 pediatric cases with an age ranging from 1 year and 7 months to 5 years and 3 months (mean age of 3 years) were retrieved and analyzed by routine histological, immunohistochemical and electron methods.

RESULTSAmong 16 patients, there were 2 type I, 7 type II and 7 type III PPB cases. Type I PPB as multilocular cystic structure, consisted of thin fibrous wall lining the respiratory epithelium, subepithelial primitive blastema or immature mesenchymal cells, with or without rhabdomyoblastic differentiation or cartilage; Type II PPB as cystic-solid tumor, comparing with type I, consisted of intracystic components with appearance of anaplastic tumor cells. Type III PPB consisted of completely solid mass, the same as the solid region of type II, had mixed pattern including blastema, undifferentiated spindle-cell proliferations and sarcomas. In addition, anaplastic tumor cells and intra-and extra- cytoplasmic eosinophilic globules were also commonly present. Epithelial components in PPB were benign. Immunohistochemical study showed primitive mesenchymal differentiation of tumors. All cases were positive for vimentin, desmin, myogenin and SMA in tumors with skeletal muscle differentiation, S-100 was positive in tumors with cartilage differentiation. All tumors were negative for synaptophysin, CD99, and CD117. Benign epithelial components were positive for AE1/AE3 and EMA. In 12 cases, electron microscopy revealed few organelles in the primitive mesenchymal cells and rich heterochromatin in mesenchymal cells, the latter also demonstrating cytoplasmic myofilament dysplasia. Nine cases had clinical follow-up ranging from 5 to 48 months, of which 4 patients died.

CONCLUSIONSPPB is a rare lung neoplasm of children under the age of 6 years, with distinct pathological morphology. PPB may arise from lung or pleura mesenchymal cells and has a poor clinical outcome.

Child, Preschool ; Cysts ; pathology ; Desmin ; analysis ; Female ; Humans ; Infant ; Lung Neoplasms ; chemistry ; pathology ; Male ; Microscopy, Electron ; Myogenin ; analysis ; Prognosis ; Pulmonary Blastoma ; chemistry ; pathology ; Sarcoma ; pathology ; Vimentin ; analysis

The identification of primary location of a metastatic tumor is a difficult diagnostic problem and sometimes can be facilitated by the use of immunohistochemical markers. Thyroid transcription factor-1 (TTF-1) is a 38-kDa nuclear homeodomain transcription factor that is expressed specifically in lung or thyroid neoplasms. Cytokeratin 20 (CK20) is a 46-kDa low-molecular-weight cytokeratin that shows restricted expression in adenocarcinomas of the gastrointestinal tract (GIT) and transitional cell carcinomas of the urinary tract. We studied the immunohistochemical expression of TTF-1 and CK20 in 68 metastatic carcinomas in cervical lymph nodes. The primary sites were the lung in 29 cases, stomach in 13, colorectum in 3, and other sites in 23. TTF-1 expression was detected in 69.0% of metastatic lung carcinomas and none in metastatic GIT carcinomas, whereas CK20 expression was detected in 68.8% of metastatic GIT carcinomas and none of metastatic lung carcinomas. TTF-1 had a specificity of 0.95 and a sensitivity of 0.69 for metastatic lung carcinoma, whereas CK20 had a specificity of 1.00 and a sensitivity of 0.69 for metastatic GIT carcinoma. These results indicate that TTF-1 and CK20 should be the first choice as a component of antibody panel to prove or to exclude the lung and GIT origin, respectively, especially in patients presenting with metastatic carcinomas of unknown primary site.
Adenocarcinoma/chemistry/pathology/secondary ; Carcinoma/chemistry/pathology/*secondary ; Gastrointestinal Neoplasms/chemistry/pathology ; Homeodomain Proteins/analysis ; Humans ; Intermediate Filament Proteins/*analysis/immunology ; Keratin-20 ; Lung Neoplasms/chemistry/pathology ; Lymph Nodes/chemistry/pathology ; Lymphatic Metastasis/*diagnosis/pathology ; Neck ; Neoplasms, Unknown Primary/chemistry/pathology ; Nuclear Proteins/*analysis/immunology ; Sensitivity and Specificity ; Transcription Factors/*analysis/immunology ; Tumor Markers, Biological/analysis

Humans ; Lung Neoplasms ; blood supply ; pathology ; Lymphatic Vessels ; pathology ; Neovascularization, Pathologic ; metabolism ; Vascular Endothelial Growth Factors ; chemistry ; metabolism ; physiology

The purpose of this study is to evaluate the clinical significance of E-cadherin expression in lung cancer. E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1). Strongly positive (++) E-cadherin tumors were classified as a type of preserved E-cadherin expression (Pr type), while the others (+, - tumors) were classified as a type of reduced E-cadherin expression (Rd type). The frequency of Pr type in squamous cell carcinomas (59.0%) was higher than Rd type. However, in adenocarcinomas, the frequency of Rd type was higher than Pr type. E-cadherin expression pattern was significantly correlated with differentiated state (Pearson correlation coefficient 0.394, p>0.001). E-cadherin expression of well-differentiated tumors was more frequently preserved than that of poorly differentiated tumors (60.0% vs. 25.9%). With regard to the correlation between E-cadherin expression and stages of lymph node metastasis in non-small cell lung cancers, the percentage of tumors with Pr type E-cadherin expression declined from 66.3% (> or = N1) to 38.6% (> or = N2), indicating that loss of E-cadherin expression is responsible for acquisition of invasive potential of lung cancer as well as the possible role of E-cadherin in the histological differentiation of lung cancer.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Cadherins/immunology ; Cadherins/biosynthesis* ; Cadherins/analysis* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/chemistry ; Female ; Human ; Immunohistochemistry ; Lung Neoplasms/pathology* ; Lung Neoplasms/metabolism ; Lung Neoplasms/chemistry ; Lymph Nodes/pathology ; Male ; Middle Age ; Predictive Value of Tests ; Prognosis

This study is to optimize the preparation process of fusion protein Fv-LDP which was expressed in the form of inclusion body and consisted of lidamycin apoprotein LDP and single-chain Fv antibody (scFv) directed against type IV collagenase. The preparation and the dissolution of inclusion body, the immobilized metal affinity chromatography of the target protein and the renaturization by stepwise dialysis were optimized by single-factor analysis or orthogonal design. In addition, the refolded fusion protein Fv-LDP was refined by Sephadex G-75 chromatography followed by fluorescence-activated cell sorter (FACS)-based saturation binding assay to measure its antigen-binding activity. After optimization of the process, the purity of fusion protein Fv-LDP existed in the inclusion body was 63.9% and the corresponding solubility was 95.7%; Under denaturing conditions, the purity of fusion protein Fv-LDP was more than 95% after the purification process. The percentage of monomeric fusion protein Fv-LDP was 60% after the refolding process, while it was further refined to 85% which was 5.6-fold higher than that of the initial refolding condition. The refined fusion protein Fv-LDP could bind to human lung adenocarcinoma PAa cells and human hepatoma BEL-7402 cells with the dissociation constants (Kd) of 0.176 micromol x L(-1) and 0.904 micromol x L(-1), respectively. The preparation process of fusion protein Fv-LDP has been successfully optimized, which provides the experimental basis for the production and future development of fusion protein Fv-LDP, and might serve as a relatively practical system for the preparation of other scFv-based proteins expressed in the form of inclusion body.
Adenocarcinoma ; metabolism ; pathology ; Aminoglycosides ; chemistry ; metabolism ; Antibiotics, Antineoplastic ; chemistry ; metabolism ; Apoproteins ; chemistry ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Collagenases ; immunology ; Enediynes ; chemistry ; metabolism ; Escherichia coli ; chemistry ; metabolism ; Humans ; Inclusion Bodies ; chemistry ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Lung Neoplasms ; metabolism ; pathology ; Protein Binding ; Recombinant Fusion Proteins ; chemistry ; metabolism ; Single-Chain Antibodies ; chemistry ; metabolism

BACKGROUNDTechnetium-99m or (99m)Tc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator.

METHODSThe cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH(2)-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with (99m)Tc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1.

RESULTSThe molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95 ± 0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of (20.75 ± 0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05 ± 0.04)% ID/g at 1.5 hpi and remained high ((2.51 ± 0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl).

CONCLUSIONThe findings suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.

Animals ; Cell Line, Tumor ; Humans ; Hydrazines ; chemistry ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Nude ; Nicotinic Acids ; chemistry ; Receptors, Somatostatin ; metabolism ; Technetium ; chemistry

AIMTo study the synthesis and antitumour activities of some aryl-substituted pteridines.

METHODSA series of aryl-substituted pteridines were synthesized from 4, 6-diamino-5-nitrosopyrimidines by cyclization with 4-aminophenylacetonitriles. The antitumour activities were tested by MTT method.

RESULTSNine new compounds (I-III) were synthesized and their structures were characterized by EA, IR, 1HNMR and MS spectra. Compounds I-III showed antitumour activities in vitro.

CONCLUSIONCompounds I-III showed remarkable antitumour activities in vitro. No interaction was determined between the title compounds and calf thymus DNA. It indicated that these compounds possibly inhibit dihydrofolate reductase (DHFR) or other enzymes on which folic acid depends.

Adenocarcinoma ; pathology ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Humans ; KB Cells ; drug effects ; Lung Neoplasms ; pathology ; Molecular Structure ; Pteridines ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo study the anti-tumor active constituents from the rhizome of Paris polyphylla var. yunnanensis.

METHODThe compounds were isolated by column chromatography with silica gel, and purified by Sephadex LH-20 columu chromafography and reverse-phase preparative, HPLC. The structures were identified by spectroscopic methods. The anti-tumor experiment in vitro, the MTT, was used to screen constituents of P. polyphalla var. yunnanensis.

RESULTSix compounds were obtained and their structures were identified as diosgenin-3-O-alpha-L-arabinofuranosyl (1-->4) -beta-D-glycopyranoside (1), pennogenin-3-O-alpha-L-arabino-furanosyl (1-->4)-beta-D-glycopyranoside (2), isorhamn etin-3-O-beta-D-glycopyranoside (3), ethyl-alpha-D-fructofuranoside (4), pennogenin-3-O-alpha-L-rhamnopyranosyl (1-->4)-[alpha-L-rhamnopyranosyl (1-->2)]-beta-D-glycopyranoside (5) and pennogenin-3-O-alpha-L-rhamnopyranosyl (1-->4)-alpha-L-rhamnopyranosyl (1-->4)-[alpha-L-rhamnopyranosyl (1-->2)]-beta-D-glycopyranoside (6).

CONCLUSIONCompounds 1-4 were isolated from this plant for the first time, compounds 3 and 4 was firstly isolated from genus Paris, compound 5 was firstly isolated from the rhizome of this plant. The pharmacological results showed that compounds 1-3, 5 and 6 showed certain inhibition, especially, the activities of compound 5 and 6 were the most significant.

Adenocarcinoma ; pathology ; Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Glycosides ; chemistry ; isolation & purification ; pharmacology ; Liliaceae ; chemistry ; Lung Neoplasms ; pathology ; Mice ; Molecular Structure ; Plants, Medicinal ; chemistry ; Rhizome ; chemistry ; Saponins ; chemistry ; isolation & purification ; pharmacology

OBJECTIVETo study the expression of caveolin-1 in primary lung cancer and its relationship with microvessel density and clinicopathologic parameters.

METHODSImmunohistochemical study for caveolin-1 and CD34 was performed on paraffin sections of 154 cases of primary lung cancer and adjacent non-neoplastic lung parenchymal tissue, as well as 36 cases with nodal metastasis. Microvessel density was analyzed by CD34 immunostaining. Western blot assay was also employed in tumor and non-neoplastic lung tissues of the 50 cases (25 cases of pulmonary squamous cell carcinoma and 25 cases of pulmonary adenocarcinoma) with fresh specimens available.

RESULTSImmunohistochemical study showed that non-neoplastic bronchial and alveolar epithelium was positive for caveolin-1 (membranous and cytoplasmic). The expression rate of caveolin-1 in lung cancer was 59.1%, which was significantly lower than that in normal lung tissues (P < 0.01). Western blot assay confirmed that the expression of caveolin-1 in pulmonary squamous cell carcinoma and adenocarcinoma was lower than in surrounding non-neoplastic lung tissues (P < 0.01). Caveolin-1 expression in pulmonary small cell carcinoma (7.1%) was significantly lower than that in non-small cell carcinoma (64.3%) (P < 0.01). Within the group of non-small cell carcinoma, the expression of caveolin-1 was much higher in patients with lymph node metastasis (P = 0.005). The expression was also higher in stage III and IV than in stage I and II disease (P = 0.042).

CONCLUSIONSThe expression of caveolin-1 is lower in lung cancer tissues than that in non-small cell carcinoma, it is also significantly correlated with tumor stage and lymph node metastasis. Caveolin-1 may play some role in the progression of pulmonary non-small cell carcinoma.

Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Caveolin 1 ; biosynthesis ; Female ; Humans ; Immunohistochemistry ; Lung ; chemistry ; metabolism ; pathology ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Microvessels ; chemistry ; metabolism ; pathology ; Middle Aged ; Neoplasm Staging ; Small Cell Lung Carcinoma ; metabolism ; pathology