Successful induction of tumor-specific cytotoxic T lymphocytes from patients with non-small cell lung cancer using CD80-transfected autologous tumor cells.

Cytotoxic T lymphocytes (CTL) against human lung cancer cells are difficult to induce by a conventional method using tumor cell stimulation probably due to an insufficiency of tumor antigens (TA) or costimulatory molecules such as CD80. We, therefore, investigated the potential of CD80-transfected tumor cells as stimulators of the in vitro induction of autologous tumor-specific CTL from regional lymph node lymphocytes in patients with lung cancer. Five non-small cell lung cancer cell lines (two adenocarcinomas, 1 squamous cell carcinoma, 1 large cell carcinoma and 1 adenosquamous cell carcinoma) were established from surgical specimens and were successfully transduced with a plasmid constructed with expression vector pBj and human CD80 cDNA, using a lipofection method.

Induction of Tumor-Specific Cytotoxic T Lymphocytes from Regional Lymph Node Lymphocytes of Human Breast Cancer.

BACKGROUND: In this study we activated breast cancer-specific cytotoxic T lymphocytes (CTL) from regional lymph node lymphocytes (RLNL) of HLA-A2-positive patients with breast cancer. METHODS: Freshly isolated RLNL were stimulated with solid phase anti-CD3 monoclonal antibody followed by expansion with recombinant interleukin-2. Subsequently, the RLNL were stimulated with an irradiated HLA 0201 breast cancer cell line,MCF-7, at a responder/stimulator ratio of 10/1 once a week for 2 weeks.

Tumor-infiltrating B-cell-derived IgG recognizes tumor components in human lung cancer.

Tumor-infiltrating lymphocytes consist predominantly of T cells, whereas B cells, plasma cells, and natural killer cells are observed with different degrees of frequency. We investigated the nature of tumor-infiltrating B lymphocytes (TIB) in human lung cancer. First, to examine the ability of immunogloblin production by TIB, cancer tissues were subcutaneously transplanted in severe combined immunodeficient mice, and the murine serum was examined for the concentration of human immunogloblin.

Fas expression in non-small cell lung cancer: its prognostic effect in completely resected stage III patients.

The aim of this study was to examine Fas expression in non-small cell lung cancer (NSCLC) and examine its correlation with clinicopathological features and prognosis. Fas expression was determined by an immunohistochemical analysis using the labelled streptavidin-biotin method from 220 paraffin specimens of completely resected primary stage I-III NSCLC. 80 (36%) of 220 cases were positive for Fas immunostaining.

Indications and operative techniques for combined aortoesophageal resection.

Combined aortoesophageal resection was performed in 8 patients, including 7 with esophageal carcinoma and 1 with aortoesophageal fistula. Aortic resection procedures included segmental resection with permanent aorto-aortic bypass (1 case), segmental resection with graft interposition (1 case), semicircumferential resection with patch aortoplasty (3 cases), wedge resection with lateral aortorrhaphy (1 case), and resection of adventitia (2 cases). Protective methods during aortic cross-clamping included one aorto-aortic permanent bypass, one subclavian-aortic bypass, and three axillo-femoral bypass.

Intratumoral neovascularization and growth pattern in early gastric carcinoma.

Background: The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects biologic characteristics of the tumor. The authors investigated the microvessel density (MVD), expression of vascular endothelial growth factor (VEGF), and growth patterns in early gastric carcinoma.

Methods: Ninety-four tissue specimens resected from patients with early gastric carcinoma invading the submucosal layer were examined.

The p53 tumor suppressor gene in anticancer agent-induced apoptosis and chemosensitivity of human gastrointestinal cancer cell lines.

Purpose: While the target of many anticancer agents has been identified, the processes leading to killing of the cancer cells and the molecular basis of resistance to the drugs are not well understood. We used human gastrointestinal cancer cell lines and examined how anticancer agents induced cell killing and how the chemosensitivity of these lines was determined.

Methods: Twelve gastrointestinal cancer cell lines were examined for the presence of either a wild-type or mutant p53 gene by direct sequencing.

Clonal analysis of a human antibody response. III. Nucleotide sequences of monoclonal IgM, IgG, and IgA to rabies virus reveal restricted V kappa gene utilization, junctional V kappa J kappa and V lambda J lambda diversity, and somatic hypermutation.

In previous work, we generated four IgM, five IgG1, and one IgA1 mAbs to rabies virus using B cells from four subjects vaccinated with inactivated rabies virus, a thymus-dependent (TD) mosaic Ag, and sequenced the mAb V(H)DJ(H) genes. Here, we have cloned the V kappa J kappa and V lambda J lambda genes to complete the primary structure of the Ag-binding site of these mAbs. While the anti-rabies virus mAb selection of VA genes (2e.

Mesenteric neurofibroma with von Recklinghausen's disease: a case report.

Mesenteric neurofibroma associated with von Recklinghausen's disease is rare. Herein, we present one such case. A 15-year-old mentally retarded Japanese boy presented with destruction of the right 2nd and 3rd ribs on a routine chest roentgenogram.

Vascular endothelial growth factor expression in non-small-cell lung cancer: prognostic significance in squamous cell carcinoma.

Background: Recently, some studies have focused on the tumor angiogenesis and its prognostic value. We studied the expression of vascular endothelial growth factor, microvessel counts, and serum concentrations of vascular endothelial growth factor to investigate their association with clinicopathologic factors and prognosis in non-small-cell lung cancer.

Methods: The expression of vascular endothelial growth factor was determined by an immunohistochemical analysis from 91 paraffin specimens of completely resected non-small-cell lung cancers using anti-growth factor polyclonal antibody.

Effects of interleukin-12 on the induction of cytotoxic T lymphocytes from the regional lymph node lymphocytes of patients with lung adenocarcinoma.

Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA-A-locus-matched tumor cells. To investigate the effect of interleukin-12 (IL-12), IL-12 was added during the stimulation of RLNL from HLA A24/adenocarcinoma patients with either autologous tumor cells or HLA A24-positive adenocarcinoma cells (PC-9) in combination with, or instead of interleukin-2 (IL-2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL-12, or the substitution of IL-2 by IL-12 was found to enhance the cytotoxic activity and the cytokine production (IFN-gamma, GM-CSF) of the CTL as compared with IL-2 alone.

The induction of cytotoxic T lymphocytes against HLA-A locus-matched lung adenocarcinoma in patients with non-small cell lung cancer.

To induce cytotoxic T lymphocytes (CTL) against non-small cell lung cancer (NSCLC) efficiently, the induction of CTL was attempted using HLA-A locus-shared allogeneic NSCLC cells. T cells derived from either tumor tissue specimens or the regional lymph nodes of patients with NSCLC were stimulated twice or three times with an HLA-A2/A24-positive NSCLC cell line (PC-9), and thereafter the cytotoxic activity was examined by 51Cr-release assay. In patients with HLA-A24/ adenocarcinoma, anti-PC-9 cytotoxicity was induced in all 6 patients tested.

Proliferative activity of esophageal carcinomas and their lymph node metastases: comparison using argyrophilic nucleolar organizer region staining.

Background: Many reports have concluded that quantification of the argyrophilic nucleolar organizer regions (AgNORs) measures proliferative activity and is a prognostic indicator in malignant disease. This retrospective study set out to evaluate the relationship between the AgNORs of the primary tumors and those of lymph node metastases in esophageal carcinoma.

Methods: Using a one-step silver staining technique, AgNORs were counted in surgical specimens from 54 patients with squamous cell carcinomas.

Prognostic value of the immunohistochemical detection of p16INK4 expression in nonsmall cell lung carcinoma.

Background: The product of the p16INK4/CDKN2/MTS1 (p16) controls the transition from the G1 phase to the S-phase in the cell cycle by inhibiting the phosphorylation of the retinoblastoma gene product. A lack of p16 expression has been reported in various cancer cell lines and tumors; however, there have been only a few reports on the prognostic significance of p16 alteration. The authors studied p16 expression in nonsmall cell lung carcinoma (NSCLC) and also examined its correlation with clinicopathologic features and prognosis.

Lymph node metastasis and relation to tumor growth potential and local immune response in advanced gastric cancer.

To evaluate the relation between the degree of lymph node metastasis and the growth potential of tumour cells and the local immune function in gastric cancer, we analyzed data on 444 patients with advanced serosally invasive gastric cancer who underwent curative gastrectomy. Tumour growth potential was evaluated based on the value proliferating cell nuclear antigen (PCNA) in the primary tumour, and dendritic cell infiltration into the tumour was determined as an indicator of local immune function. The values of PCNA labeling in the primary tumour increased and the infiltration of dendritic cells into the tumour decreased in relation to the extent of lymph node metastasis.

Overexpression of p53 is associated with growth pattern and prognosis in advanced gastric cancer.

Background/aims: The growth pattern of advanced gastric carcinoma, based on volumetric analysis, is closely associated with the biological characteristics of tumors, including DNA ploidy, and is an important prognostic factor. Abnormality of the p53 tumor suppressor gene plays an important role in alteration of cells and possibly leads to cancer development.

Materials And Methods: Expression of tumor suppressor gene p53 was investigated immunohistochemically in the primary lesion of 196 patients with advanced gastric cancers, and the relationship of p53 immunopositivity with the growth pattern and prognosis was analyzed.

Expression of multidrug-resistance-associated protein (MRP) and chemosensitivity in human gastric cancer.

Evidence has accumulated that, in addition to the MDR1 gene-coded P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP) also mediates the multidrug resistance (MDR) of various human tumors. In the case of gastric cancer, there is little or no involvement of P-glycoprotein, and the mechanisms of MDR remain to be understood. To search for a possible relationship between expression of MRP and sensitivity to anti-cancer agents in gastric cancer, 4 gastric cancer cell lines, 43 human gastric carcinomas and 17 adjacent normal gastric tissue samples were analyzed.

Recurrences and related characteristics of gastric cancer.

We analysed data on 1117 patients with gastric cancer who were treated by curative resection. Attention was focused on invasion and a recurrence of the cancer. Based on a univariate analysis, death following a recurrence and prognosis were related to age of the patients, size of the tumour, tumour location, tumour tissue differentiation, growth pattern, depth of invasion, lymphatic and vascular invasion and lymph node metastasis.

An integrated microsatellite length analysis using an automated fluorescent DNA sequencer.

Analyzing microsatellite instability (MI) in malignant tumors is thought to be useful for screening cancer patients to identify those patients with a higher risk of developing second malignant tumors. In this paper, we report a new, accurate, and efficient method of detecting MI using an automated fluorescent DNA sequencer and a computer that automatically calculates the size, height, and area of each fluorescent product, making it possible to assess MI more accurately and more rapidly. The primers for amplification of each microsatellite locus are labeled by two different fluorescent dyes, rox (red) and fam (blue).

Argyrophilic nucleolar organizer region in endoscopically obtained biopsy tissue: a useful predictor of nodal metastasis and prognosis in carcinoma of the stomach.

Background: Argyrophilic nucleolar organizer region (AgNOR) staining is a simple and economical technique for investigating proliferative activity. We examined AgNOR measured in biopsy specimens of carcinoma of the stomach in humans.

Study Design: Argyrophilic nucleolar organizer region staining was done on 76 biopsy specimens and corresponding resected cancer tissues.

Surgical treatment for gastric carcinomas with concomitant hepatic metastasis.

Background/aims: We have reviewed our experience with gastric cancer patients having synchronous liver metastasis in an attempt to clarify how to treat such patients.

Patients And Methods: In 116 patients with gastric cancer metastatic to the liver, evaluations were executed to find an effective treatment. Fourteen received gastrectomy plus hepatic resection (Group A), 68 gastrectomy alone (Group B), and 34 non-resected (Group C).

Macroscopic appearance and biological character of gastric cancer invading the muscularis propria.

Background/aims: The natural history of gastric cancer, as to how an early gastric cancer develops into an advanced lesion, is still an open question. In this study, we focused on the gastric cancer invading the muscularis propria, and analyzed the relationship between gross appearance and the biological characteristics of gastric cancer.

Materials And Methods: One hundred and forty six patients with gastric cancer invading the muscularis propria (pm) were studied with special reference to the macroscopic appearance of the primary tumor; Borrmann type vs.

Age-related characteristics of gastric carcinoma in young and elderly patients.

Background: The clinicopathologic features of young and elderly patients with gastric carcinoma have been analyzed.

Methods: We analyzed the data from 174 patients with gastric carcinoma age 40 years and younger and from 356 patients with gastric carcinoma age 70 years and older who were surgically treated at the Department of Surgery II, Kyushu University, Japan.

Results: The rate of multiple gastric carcinomas was 2.

Microvessel quantification and its possible relation with liver metastasis in colorectal cancer.

Background: Several studies have proven the usefulness of microvessel quantification as a prognostic factor for patients with various malignant tumors. The aim of this paper was to clarify the relationship between microvessel density (MVD) as a parameter of tumor angiogenesis and liver metastasis in colorectal cancer.

Methods: A total of 175 patients with advanced colorectal cancer were evaluated (58 with concurrent liver metastases).

Multidrug resistance-associated protein expression in clinical gastric carcinoma.

Background: We examined the relationship between the expression of a multi-drug resistance-associated protein (MRP) and the biologic factors regarding invasion and metastasis of human gastric cancer.

Methods: In 75 patients with gastric cancer, the expression of MRP was immunohistochemically investigated and the expression of MRP mRNA was also detected using reverse transcription PCR (RT-PCR). Sensitivity to the anticancer agents, cisplatin (CDDP), doxorubicin (DXR), etoposide (VP-16), and mitomycin C (MMC) was examined using the MTT {3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl[2H]-tetra-zolium bromide} assay.