Human kallikrein gene 5 (KLK5) expression by quantitative PCR: an independent indicator of poor prognosis in breast cancer.

Background: KLK5 is a newly discovered human kallikrein gene. Many kallikrein genes have been found to be differentially expressed in various malignancies, and prostate-specific antigen (PSA; encoded by the KLK3 gene) is the best tumor marker for prostate cancer. Like the genes that encode PSA and other kallikreins, the KLK5 gene was found to be regulated by steroid hormones in the BT-474 breast cancer cell line.

Serum levels of CA 125 and TPS during treatment of ovarian cancer.

Two hundred and sixty ovarian cancer patients (including all FIGO stages) were enrolled in a prospective multicentre study. In this interim study we analyzed 206 patients receiving combined chemotherapy for at least 3 courses for two-year overall survival (OS). CA 125 and TPS were applied for monitoring treatment and the relationship between marker levels, marker changes and clinical assessments was established.

Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies.

The Ku70/80 heterodimer is the regulatory subunit of the DNA-dependent protein kinase (DNA-PK) and its DNA-binding activity mediates DNA double-strand breaks repair. Although Ku80 was recently proposed as a caretaker gene involved in the control of genome integrity, no data are available on Ku70/80 DNA-binding activity in human tumors. Heterodimer DNA-binding activity and protein expression were assayed by electrophoretic-mobility-shift-assay (EMSA) and Western blot analysis, in nuclear and cytoplasmic extracts from eight breast, seven bladder primary tumors and three metastatic nodes from breast cancers.

Codon 89 polymorphism in the human 5 alpha-reductase gene in primary breast cancer.

The enzyme human steroid 5-alpha reductase type II (SRD5A2) and androgen receptor (AR) are critical mediators of androgen action, suggesting a potential role in hormonally related cancers. The SRD5A2 gene harbours two frequent polymorphic sites, one in the coding region, at codon 89 of exon 1, where valine is substituted by leucine (V89L) and the other in the 3' untranslated region (3' UTR) where a variable number of dinucleotide TA repeat lengths exists. The V89L polymorphism is known to alter the activity of this enzyme.

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.

Objective: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients.

Methods: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses.

Sentinel lymph node and breast cancer staging: final results of the Turin Multicenter Study.

Aim Of The Study: Validation of the sentinel node (SN) technique in breast cancer by means of lymphoscintigraphy.

Materials And Methods: From December 1996 to January 1999 102 T1-T2 breast carcinoma cases were recruited in Turin. 99mTc-human serum albumin colloids were injected subdermally the day before surgery (mean activity, 5.

Breast cancer prognostic significance of a single nucleotide polymorphism in the proximal androgen response element of the prostate specific antigen gene promoter.

Prostate Specific Antigen (PSA) expression by breast epithelial cells is associated with favorable breast cancer prognosis. In preliminary studies, we found that a nucleotide variation (G-->A) at position -158 in the androgen response element (ARE-1) of the PSA promoter was present in four out of 9 breast tumors examined and in a breast carcinoma cell line. We have now determined the nucleotide composition at position -158 of DNA extracted from 148 well-characterized breast tumors and compared tumor genotype with that of controls without cancer, with tumor PSA concentration and with clinicopathological variables, overall survival and disease free survival.

Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian suppression as adjuvant treatment of estrogen receptor-positive pre-/perimenopausal breast cancer patients: results of the Italian Breast Cancer Adjuvant Study Group 02 randomized trial. boccardo@hp380.ist.unige.it.

Purpose: To compare the efficacy of chemotherapy versus that of tamoxifen plus ovarian suppression in pre-/perimenopausal estrogen receptor-positive patients with early breast cancer.

Patients And Methods: Patients were randomly assigned to receive either six cycles of a standard regimen of cyclophosphamide 100 mg/m(2) orally days 1 to 14, methotrexate 40 mg/m(2) intravenously (IV) days 1 and 8, and fluorouracil 600 mg/m(2) IV days 1 and 8 (CMF), with all drugs restarted on day 29, or 5 years of tamoxifen, 30 mg/d, plus ovarian suppression with surgical oophorectomy, ovarian irradiation, or monthly goserelin 3.6-mg injections.

Shorter CAG repeat length in the androgen receptor gene is associated with more aggressive forms of breast cancer.

The androgen receptor (AR) is a transcription factor mediating the action of androgens. The AR gene is localized on chromosome X and it contains a series of CAG trinucleotide repeats. The length of the CAG repeats varies among individuals and this polymorphism is believed to be related to AR transcriptional activity.

TA repeat polymorphism of the 5alpha-reductase gene and breast cancer.

There is increasing evidence that androgens play a significant role in the development and progression of breast cancer. 5alpha-Reductase (SRD5A2) is an enzyme that is expressed in androgen-dependent tissues, and it catalyzes the reduction of testosterone to its more bioactive form, dihydrotestosterone, which then transactivates a number of genes. One of these genes encodes for prostate-specific antigen (PSA), a favorable prognostic factor in breast cancer.

p53 gene mutation, tumor p53 protein overexpression, and serum p53 autoantibody generation in patients with breast cancer.

Objectives: Autoantibodies against the p53 tumor suppressor protein have been detected in the serum of a proportion of patients with various cancers. The generation of such antibodies has been proposed to be due to either tumor p53 protein accumulation or to the type of p53 gene mutation. These hypotheses are examined in the present study.

Serum total and free prostate-specific antigen for breast cancer diagnosis in women.

Prostate-specific antigen (PSA) is a serine protease expressed at high levels in prostate epithelium, and elevated PSA in serum is a well-established marker of prostate cancer. Recently, the relative proportions of free PSA and PSA complexed to the serine protease inhibitor alpha 1-antichymotrypsin have become important variables in distinguishing between prostate cancer and benign prostatic hyperplasia. Numerous studies have demonstrated the production of PSA in female tissues such as the breast, and low levels of PSA are present in female sera.

HRT, breast and endometrial cancers: strategies and intervention options.

The demand for hormone replacement therapy (HRT) by women who enter the menopause is rapidly increasing in all developed countries. The concern that HRT may enhance morbidity and mortality from malignant diseases still limits the widespread adoption of hormonal treatments. Overall, epidemiological data on cancer incidence and HRT are reassuring, although long-term or inappropriate therapies may slightly increase the risk of developing malignant diseases.

Prognostic significance of CA 125 and TPS levels after chemotherapy in ovarian cancer patients.

The analysis of survival data of patients with epithelial ovarian cancer proved that both CA 125 and TPS were good markers for clinical outcome prediction. Patients receiving chemotherapy were analyzed for 2-year overall survival (OS). Kaplan-Meier survival analysis showed highly significant differences in OS between patients with stage I+II (survival for 2 years 68%) and stage III+IV (survival for 2 years 33%; p = 0.

Immunoenzymatically determined pepsinogen C concentration in breast tumor cytosols: an independent favorable prognostic factor in node-positive patients.

The aim of this study was to determine the concentration and to evaluate the prognostic value of pepsinogen C (PepC) in breast cancer patients. PepC is an aspartic proteinase that is involved in the digestion of proteins in the stomach and is also synthesized by a subset of human breast tumors. PepC concentrations were measured with a highly sensitive immunofluorometric assay, which uses two monoclonal antibodies that are specific for PepC and has a detection limit of 0.

Prostate specific antigen molecular forms in breast cyst fluid and serum of women with fibrocystic breast disease.

We have analyzed matched serum and breast cyst fluid samples for total PSA from 148 patients with fibrocystic breast disease. We have also determined the molecular forms of PSA (free PSA and PSA bound to alpha1-antichymotrypsin) in 78 breast cyst fluid samples. We found that total PSA can be detected in all cyst fluids and in about 75% of female sera.

Quantification of pepsinogen C and prostaglandin D synthase in breast cyst fluid and their potential utility for cyst type classification.

Objective: To quantify pepsinogen C (PEPC) and prostaglandin D synthase (PGDS) in breast cyst fluid and examine if these two parameters can be used for breast cyst type classification.

Design And Methods: We quantified PEPC and PGDS in 92 and 50 breast cyst fluids, respectively, using previously established immunofluorometric procedures. We then examined if the levels of PEPC or PGDS correlate with the type of cyst or with other clinicopathological variables.

Italian Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group Trials. GROCTA Trials.

The first GROCTA trial compared 5-year tamoxifen treatment to ten chemotherapy cycles in a group of 504 pre-/post-menopausal, node-positive, ER-positive breast cancer patients. This study also included an arm combining tamoxifen with chemotherapy. Fifteen-year results showed no difference between tamoxifen and tamoxifen plus chemotherapy, while both treatments were significantly superior to chemotherapy alone.

Overexpression of the RON gene in human breast carcinoma.

Constitutive activation of the RON gene, known to code for the tyrosine-kinase receptor for Macrophage Stimulating Protein (also known as Scatter Factor 2), has been shown to induce invasive-metastatic phenotype in vitro. As yet, nothing is known about the expression of this novel member of the MET-oncogene family in spontaneously occurring human cancers. Here we report that Ron is expressed at abnormally high levels in about 50% primary breast carcinomas (35/74 patients).

Immunofluorometrically determined p53 accumulation as a prognostic indicator in Italian breast cancer patients.

The prognostic value of p53 protein accumulation in breast cancer, especially as detected by methods other than immunohistochemistry, has not been established unequivocally. A sensitive immunofluorometric assay of p53 protein employing DO-1 and CM-1 antibodies was used in this study to assay extracts of 171 breast carcinomas from northern Italy. p53 over-expression, demonstrated in 36 (21%) tumours, was associated with lack of oestrogen receptor (ER) expression but was not related to patient age, stage, lymph node status, tumour size, histologic type, grade or progesterone receptor (PR) expression status in contingency tables.

Clinical and ethical issues in the diagnosis of hereditary breast cancer (review).

A small subset of breast and ovarian cancers is related to the mutation of dominant susceptibility genes. The recent isolation of BRCA1 and BRCA2 has created great interest and expectations among members of families with a positive history for breast/ovarian cancer. We reviewed the literature to explore the clinical implications of genetic testing for BRCA1 and BRCA2 mutations among high risk women.

Molecular forms of prostate-specific antigen in the serum of women with benign and malignant breast diseases.

Using a highly sensitive immunofluorometric procedure, we measured the total prostate-specific antigen (PSA) concentration in 632 sera obtained from female blood donors and women with idiopathic hirsutism, breast cancer or benign breast diseases. A total of 50 sera with total PSA > 15 ng l(-1) were fractionated by high-performance liquid chromatography (HPLC) in order to resolve the two immunoreactive molecular forms, i.e.

Progestins and breast cancer risk.

There is still no clear account on the role that progestins play in human breast cancer, and the issue continues to be debated. The effects of progestins on breast cell proliferation have been investigated in a number of different experimental systems with conflicting results. Progesterone has been reported to both stimulate and inhibit the growth of experimental mammary tumors, depending upon the dose and the experimental models.