Tyrosine kinase inhibitors.

Over the last ten years, several new and therapeutically relevant cancer drugs targeting tyrosine kinases signaling pathways have been developed. Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available, well-tolerated, worldwide approved drugs for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumors and chronic myeloid leukemia. This comprehensive review focuses on the most relevant members of the first and the second generation TKIs designed to interact with receptor and nonreceptor TKs.

Molecular mechanisms of endocrine resistance and their implication in the therapy of breast cancer.

The use of endocrine agents is a safe and effective treatment in the management of hormone-sensitive breast cancer. Unfortunately, sooner or later, tumor cells develop resistance to endocrine manipulation making useless this approach. During the last decade, new molecules and intracellular signaling pathways involved in endocrine resistance have been identified.

A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds.

The anti-inflammatory, antiangiogenic, anticoagulant, and antiadhesive properties of fucoidans obtained from nine species of brown algae were studied in order to examine the influence of fucoidan origin and composition on their biological activities. All fucoidans inhibited leucocyte recruitment in an inflammation model in rats, and neither the content of fucose and sulfate nor other structural features of their polysaccharide backbones significantly affected the efficacy of fucoidans in this model. In vitro evaluation of P-selectin-mediated neutrophil adhesion to platelets under flow conditions revealed that only polysaccharides from Laminaria saccharina, L.

Changes of topoisomerase IIalpha expression in breast tumors after neoadjuvant chemotherapy predicts relapse-free survival.

Purpose: To assess the value of changes in the expression of topoisomerase IIalpha (TopoII) and the proto-oncogene erbB-2 (HER-2) as predictors of relapse-free survival in women with operable breast cancer treated with anthracycline-based neoadjuvant chemotherapy.

Patients And Methods: Seventy-seven patients with primary breast cancer who had undergone neoadjuvant anthracycline-based chemotherapy were included in the present study. TopoII and HER-2 were measured by immunohistochemistry in prechemotherapy and postchemotherapy (at the time of surgery) tumor specimens, and the value of their changes as predictors of relapse-free survival were evaluated by Kaplan-Meier and Cox proportional hazard regression analyses.

Adhesion to 90K (Mac-2 BP) as a mechanism for lymphoma drug resistance in vivo.

A cell-adhesive protein of the human serum, 90K binds galactin-3, beta1-integrins, collagens, and fibronectin, and it is of importance in cell-cell and cell-extracellular matrix adhesion. Serum 90K levels in 137 patients with lymphoma were measured by enzyme-linked immunosorbent assay. Compared with healthy controls, pretreatment serum 90K levels in patients with lymphoma were elevated (P <.

Concentrations of galectin-3 in the sera of normal controls and cancer patients.

Galectin-3, a member of the beta-galactoside-binding animal lectins, has been implicated in tumor invasion and metastasis. Using an immunoligand assay, we assessed the circulating levels of galectin-3 in sera from cancer patients as well as from healthy controls. Low serum levels of galectin-3 were detected in healthy individuals (median, 62 ng/ml; range, 20-313 ng/ml; 95th percentile, 184.

Human milk 90K (Mac-2 BP): possible protective effects against acute respiratory infections.

Eighty-six children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk 90K, a secreted glycoprotein with immune-stimulatory properties, on development of acute respiratory infections (ARI). The level of human milk 90K was inversely related to episodes of ARI (r = - 0.34; P = 0.

A phase II study of neoadjuvant chemotherapy with cisplatin epirubicin and VP-16 for stage III unresectable non-small cell lung cancer.

Background: The survival rate for surgically resected stage III N2 non-small cell lung cancer (NSCLC) patients is less than 10%.

Methods: A phase II study of cisplatin, epirubicin, and VP-16 (PEV) was undertaken in an attempt to improve the curative potential of surgery. Forty-one patients with stage III N2 NSCLC received 3 cycles of pEV.

90K (Mac-2 BP) predicts CD4 decline in human immunodeficiency virus-infected patients with CD4 counts above 200 x 10(6) cells/L.

Objective: To evaluate the ability of serum levels of 90K, previously reported as a progression marker of human immunodeficiency virus infection, to predict the future rate of CD4 lymphocyte decline.

Design: Retrospective analysis of data from outpatients enrolled in a multi-institutional study.

Patients: One hundred five human immunodeficiency virus-positive intravenous drug users who had at least six serial CD4 lymphocyte measurements and starting CD4 levels of 200 x 10(6) cells/L or higher.

90K (MAC-2 BP) gene expression in breast cancer and evidence for the production of 90K by peripheral-blood mononuclear cells.

The tumor-derived antigen 90K (Mac-2 BP) is a widely expressed, secreted glycoprotein found in the serum of healthy individuals and at elevated levels in the serum of patients with breast cancer and other types of cancer. The precise function of 90K, particularly in the context of tumor-host relationships, has not yet been established. In this study, the clinical significance of 90K mRNA expression was studied in relation to other established prognostic parameters in 86 patients with primary breast carcinoma.

The immune stimulatory protein 90K increases major histocompatibility complex class I expression in a human breast cancer cell line.

90K is a widely expressed, secreted 90 kDa human serum protein found both in normal individuals and at elevated levels in the serum of cancer patients. Functional characterization revealed stimulatory effects of 90K on immune defense systems, such as natural killer and lymphokine-activated killer cell activity. Recently, experiments have shown that 90K expression in several tumor cell lines inversely correlates with tumor formation in athymic mice.

A phase I study of 5-day continuous venous infusion of carboplatin at circadian rhythm-modulated rate compared with constant rate.

The circadian rhythm-modulated delivery of anticancer drugs has been shown to reduce toxicity and improve anticancer efficacy. The aim of this phase I trial was to compare the feasibility and tolerability of carboplatin (CBDCA) administered at circadian-modulated or flat infusion rate in 24 patients with advanced cancer. Each treatment cycle consisted of a 5-day continuous intravenous infusion of CBDCA, to be repeated at 28-day intervals.

The 90K tumor-associated antigen and clinical progression in human immunodeficiency virus infection.

We investigated the possibility that a secreted glycoprotein of approximately 90,000 daltons, termed 90K and identified as a member of the protein superfamily characterized by the scavenger receptor cysteine-rich (SRCR) domain, might have value as a predictor of progression to acquired immunodeficiency syndrome (AIDS) in subjects infected with the human immunodeficiency virus (HIV). Among 488 HIV-seropositive intravenous drug users with a median follow-up of 32.5 months, high levels of serum 90K at baseline proved to be a significant predictor of faster progression to AIDS, either as a continuous variable (log 90K; p < 0.

Chronomodulated infusion of 5-fluorouracil, folinic acid and carboplatin in colorectal cancer: a pilot study.

We investigated if chronomodulated infusion of fluorouracil, folinic acid in combination with carboplatin shows antitumor efficacy in patients advanced metastatic colorectal cancer. Thirteen patients entered into the study. Each treatment cycle consisted of a 5 day course of continuous venous infusion of 5-fluorouracil (5-FU; 500 mg/m2/die), folinic acid (FA; L-form, 150 mg/m2/die) and carboplatin (CBDCA; the dose being calculated according to the Calvert's formula).

A phase I study of recombinant interferon-alpha administered as a seven-day continuous venous infusion at circadian-rhythm modulated rate in patients with cancer.

A Phase I trial of interferon-alpha (IFN-alpha) administered at circadian-rhythm modulated rate was carried out to evaluate maximum tolerated dose (MTD) and toxicity in patients with advanced malignancies. Recombinant IFN-alpha-2b was administered as a 7-day continuous venous infusion with maximum delivery between 6 p.m.

Elevated serum levels of a 90,000 daltons tumor-associated antigen in cancer and in infection by human immunodeficiency virus (HIV).

Levels of a 90,000 daltons monoclonal antibody-defined tumor-associated antigen, termed 90K, were measured in the serum from 649 patients with various types of cancer and 1215 patients infected by the human immunodeficiency virus (HIV). Significantly increased 90K serum levels (12.1 +/- 0.

Prognostic value of a novel circulating serum 90K antigen in breast cancer.

Monoclonal antibody SP-2 to the tumour-associated antigen 90K was generated by immunisation with conditioned medium of human breast cancer cells. We investigated whether circulating levels of 90K can influence the prognosis of patients with breast cancer. Serum samples were obtained from 425 patients with histologically proven breast cancer with no clinical evidence of disease after surgery (NED) and in 310 patients with metastatic disease.

[Androgen deprivation in benign prostatic hypertrophy].

Benign prostatic hypertrophy is the cause of urinary outflow obstruction in the majority of men older than 50 years. Even if the pathophysiology of BPH is multifactorial, its development needs testicular androgens and aging. Androgen deprivation is the only approach that may reduce the hyperplastic state.