Identification of a 17-protein signature in the serum of lung cancer patients.

Early detection of lung cancer may potentially help to improve the outcome of this fatal disease. Currently, no satisfactory laboratory tests are available to screen for this type of cancer. The aim of this study was to improve diagnostic procedures for lung cancer through the discovery of serum biomarkers using SELDI-TOF MS (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry).

Epidermal growth factor receptor-related tumor markers and clinical outcomes with erlotinib in non-small cell lung cancer: an analysis of patients from german centers in the TRUST study.

Introduction: Relationships between clinical outcomes and epidermal growth factor receptor (EGFR)-related tumor markers were investigated in patients with advanced non-small cell lung cancer.

Methods: Patients with stage IIIB/IV non-small cell lung cancer (0-2 prior regimens) received erlotinib (150 mg PO per day). Response and survival were evaluated, and tumor samples were assessed by immunohistochemistry (EGFR, phosphorylated mitogen-activated protein kinase, and phosphorylated AKT protein expression), fluorescence in situ hybridization (FISH; EGFR gene copy number), and DNA sequencing (EGFR, KRAS gene mutations).

Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer.

Paclitaxel poliglumex (PPX), a macromolecule drug conjugate linking paclitaxel to polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel. Patients with non-small-cell lung cancer (NSCLC) who had received one prior platinum-based chemotherapy received 175 or 210 mg m(-2) PPX or 75 mg m(-2) docetaxel. The study enrolled 849 previously treated NSCLC patients with advanced disease.

[Multimodal treatment of non small cell lung cancer].

The primary treatment of lung cancer depends on tumor stage. Chest CT scan and bronchoscopy are used to define the TNM stage and resectability. In case of lung cancer without mediastinal lymph node enlargement or direct mediastinal involvement (clinical stage I-IIb + T3N1) surgical treatment is recommended.

DNA methylation disturbances as novel therapeutic target in lung cancer: preclinical and clinical results.

The prognosis of lung cancer is very much limited by the difficulties of diagnosing early stage disease amenable to surgery. Thus, novel diagnostic and therapeutic approaches are urgently needed for this common type of cancer. Recently, epigenetic alterations of tumor cells have been defined for a multitude of tissues and genes.

Impact of [18F]FDG-PET on the primary staging of small-cell lung cancer.

Purpose: The purpose of this study was to evaluate the impact of [18F]fluorodeoxy-D-glucose positron emission tomography (FDG-PET) on the primary staging of patients with small-cell lung cancer (SCLC).

Methods: FDG-PET was performed in 120 consecutive patients with SCLC during primary staging. In addition, brain examinations with both FDG-PET and cranial magnetic resonance imaging (MRI) or computed tomography (CT) were performed in 91 patients.

Outcome of adult patients with T-lymphoblastic lymphoma treated according to protocols for acute lymphoblastic leukemia.

We treated 45 adult patients with T-lymphoblastic lymphoma (T-LBL) (age range 15-61 years) with 2 protocols designed for adult acute lymphoblastic leukemia (ALL). An encouraging cure rate of 90% was recently reported for T-LBL in children treated with a similar approach. In our study, an 8-drug standard induction was administered over 8 weeks including prophylactic cranial (24 Gy) and mediastinal irradiation (24 Gy) followed by consolidation and reinduction therapy.

FDG-PET imaging for the staging and follow-up of small cell lung cancer.

The staging procedures for small cell lung cancer do not differ appreciably from those for other forms of lung cancer. For practical purposes, the TNM stages are usually collapsed into a simple binary classification: limited disease and extensive disease. This study was performed to answer the question of whether fluorine-18 labelled 2-deoxy-2-D-glucose positron emission tomography (FDG-PET) imaging permits appropriate work-up (including both primary and follow-up staging) of patients presenting with small cell lung cancer, as compared with currently recommended staging procedures.

[What is the value of neoadjuvant therapy in bronchial carcinoma?].

Neoadjuvant chemotherapy is obligatory for small-cell lung cancer. When combined with radio-therapy, it reduces the incidence of recurrence and increases the survival rate to a level similar to that seen in non-small-cell lung cancer. Preliminary results suggest that complete remissions (3-year-survival rate 56%) can be achieved through the use of chemotherapy, possibly including high-dose chemotherapy for advanced stage III A cancer.

Lymphotoxin-alpha is an autocrine growth factor for chronic lymphocytic leukemia B cells.

Lymphotoxin-alpha (LT), also called TNF-beta, which belongs to the 'TNF family' was originally isolated from a lymphoblastoid cell line. LT enhances the proliferation of activated B cells and augments B cell proliferation induced by IL-2. It functions as an autocrine growth factor for EBV-infected B cell lines and has been implicated in the pathogenesis of B cell malignancies.

Poor prognosis of prethymic phenotype acute lymphoblastic leukemia (pre-T-ALL).

Pre-T-ALL is an important subgroup of ALL with clinical features different from adult T-ALL. Expression of intracytoplasmic CD3 represents the earliest marker for the prethymic phenotype. We studied four consecutive adult patients with this phenotype.

High levels of circulating soluble receptors for tumor necrosis factor in hairy cell leukemia and type B chronic lymphocytic leukemia.

The presence of soluble tumor necrosis factor (TNF) binding proteins (BP) was investigated in the sera of healthy volunteer blood donors and cancer patients. Two distinct types of TNFBP, types A and B, which are immunologically related to the cellular 75-kD TNF receptor (TNFR) and the cellular 55-kD TNFR, respectively, were assessed by immunoassays using nonblocking anti-receptor antibodies and 125I-recombinant human TNF alpha. As compared to the titers observed in 25 healthy controls, TNFBP types A and B titers were found to be elevated in almost all sera obtained from patients with underlying malignant disease.

Human interleukin-7 induces proliferation of neoplastic cells from chronic lymphocytic leukemia and acute leukemias.

The biologic effects of interleukin-7 (IL-7) and the expression of specific IL-7 membrane receptors on isolated neoplastic cells from previously untreated patients with chronic lymphocytic leukemia as well as acute leukemias were investigated in vitro. Leukemic cells were incubated for up to 6 days with various concentrations of IL-7 (0.01 to 2,000 U/mL).

Spontaneous interferon-alpha antibodies in a patient with pure red cell aplasia and recurrent cutaneous carcinomas.

High-titered spontaneous interferon (IFN) antibodies were detected in a patient with pure red cell aplasia (PRCA), a benign mediastinal tumor, and recurrent cutaneous carcinomas. The circulating IFN antibodies reacted broadly with various human IFN-alpha subtypes (20-140 x 10(3) neutralizing units/ml serum) but not with IFN-beta or IFN-gamma, and they neutralized the antiviral activity of the patient's endogenous IFN-alpha. The IFN-alpha-binding activity was restricted to the IgG1 subclass in a nonmonoclonal manner.

Pharmacokinetics and biological activity in subcutaneous long-term administration of recombinant interferon-gamma in cancer patients.

We have investigated the pharmacokinetics, tolerance, and biological activity of recombinant human interferon-gamma (rHuIFN gamma) administered subcutaneously to cancer patients. Twenty-one patients with lymphoma and metastatic cancer received rHuIFN gamma (in doses of 0.1, 0.

Receptors for tumor necrosis factor on neoplastic B cells from chronic lymphocytic leukemia are expressed in vitro but not in vivo.

Recombinant tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces proliferation of neoplastic B cells from patients with chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms involved in regulating TNF responsiveness, we have examined TNF receptor expression on neoplastic B-CLL cells. We have demonstrated that freshly isolated neoplastic B cells from patients with CLL did not express TNF receptors.

Tumor necrosis factor-alpha, but not lymphotoxin, stimulates growth of tumor cells in hairy cell leukemia.

We investigated the effect of recombinant tumor necrosis factor-alpha (rTNF-alpha) and recombinant lymphotoxin (rLT) in the growth modulation of purified hairy cell leukemia (HCL) cells. In response to rTNF-alpha, HCL cells from five of eight patients showed a 3 to 23-fold thymidine incorporation above their unstimulated controls. The effect was time and dose dependent with a maximum between 10 and 25 ng/ml rTNF-alpha after 120-hr incubation.

Antilymphocyte immunoglobulins stimulate peripheral blood lymphocytes to proliferate and release lymphokines.

Five different preparations of antilymphocyte immunoglobulins (ATG) and antithymocyte immunoglobulins (ALG) with good or little clinical response were compared for their hematopoietic and immunological activities. All ATG/ALG lots demonstrated complement-mediated cytotoxicity on peripheral blood mononuclear cells. They had different titers of antibody specificities against lymphocyte cell membrane antigens.

Elevated plasma cortisol levels during interferon-gamma treatment.

We investigated plasma levels of cortisol and ACTH in 9 patients with advanced metastatic tumors before and during treatment with interferon-gamma (IFN-gamma), 2-4 h after administration of IFN-gamma there was a sharp rise in plasma cortisol levels. The rise coincided with the onset of fever. Highest cortisol levels were reached 4-6 h after IFN-gamma injections, whereas IFN-gamma serum levels peaked 6-10 h after the IFN-gamma injections.

Tumor necrosis factor induces proliferation of neoplastic B cells from chronic lymphocytic leukemia.

The biologic effects of recombinant tumor necrosis factor-alpha (rTNF-alpha) and the expression of specific TNF membrane receptors on isolated neoplastic B cells from previously untreated patients with chronic lymphocytic leukemia (CLL) were investigated in vitro. Isolated B cells were incubated up to six days with various concentrations of rTNF-alpha (0.1 to 100 ng/mL).

Different antitumor mechanisms of interferon-alpha in the treatment of hairy cell leukemia and renal cell cancer.

There is increasing evidence for the therapeutic effectiveness of Interferon-alpha (IFN-alpha) in malignant diseases. However, the antitumor mechanisms of IFN-alpha are not known. Using two examples, hairy Cell leukemia (HCL) and renal cell cancer (RCC), it is shown that the requirements for successful IFN-alpha therapy of HCL and RCC are different.

Lymphokines as inhibitors of hematopoietic cell proliferation.

Although the identification of lymphokines negatively affecting hematopoiesis is rapidly increasing, efforts to precisely define their action even in vitro have become more and more complicated. Studies of lymphokine abnormalities in aplastic anemia exemplify the modest contribution of experimental hematology to permit access to possible pathogenic mechanisms of hematopoietic failure syndromes. Nevertheless, these results help in the interpretation of clinical observations and to develop alternative therapeutic concepts.