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S Lehrer

Publications and source records attributed to S Lehrer.

At least 19 recordsLinked to original sources

Serum interleukin-8 is elevated in men with prostate cancer and bone metastases.

Aalinkeel et al. (1) have recently reported that gene expression of angiogenic factors correlates with metastatic potential of prostate cancer cells. The rationale for the study of Aalinkeel et al. is that a variety of growth factors, among them interleukin-8 (il-8), can induce angiogenesis (2). Further, parathyroid hormone related peptide (PTHrP) acts to induce il-8 production in prostate cancer cells via an intracrine pathway independent of its classical nuclear localization sequence. This novel pathway could mediate the effects of PTHrP on the progression of prostate cancer (3). We measured il-8 in the serum of 39 men with biopsy-proven prostate cancer. Their average age was 69 +/- 9 (mean +/- SD). Serum il-8 was measured with an automated chemiluminometric high sensitivity il-8 protein assay (Immulite, Diagnostic Products Corporation, Los Angeles, CA). We noted a significant elevation of il-8 in men with bone metastases, diagnosed by Tc-99 MDP bone scan, when compared to men with localized disease (Figure 1). Aalinkeel et al. found that il-8 was significantly higher in the more metastatic PC-3 and DU-145 prostate cancer cell lines, when compared to the poorly metastatic LnCAP cells. The results of our study of il-8 in men with prostate cancer support the findings of Aalinkeel et al. Therefore, new anti-angiogenic therapies targeting specific genes controlling prostate tumor metastasis may be of benefit in treating prostate cancer.

Aged↗

Putative protein markers in the sera of men with prostatic neoplasms.

OBJECTIVE: To describe the preliminary identification of serum proteins that may be diagnostic markers in prostate cancer. PATIENTS AND METHODS: The study included 11 men referred for treatment of localized prostate cancer, 12 with benign prostatic hyperplasia (BPH) and 12 disease-free controls. For serum protein analysis, the protein-chip array surface-enhanced laser desorption/ionization (SELDI) technique was used (Ciphergen Biosystems, Fremont, CA). SELDI combines protein-chip technology with time-of-flight mass spectrometry, and offers the advantages of speed, simplicity and sensitivity. RESULTS: Three protein peaks were identified in the serum of men with prostate cancer and BPH, but not in controls, with relative molecular masses of 15.2, 15.9 and 17.5 kDa. These three proteins were significantly associated with BPH and prostate cancer when compared with controls (P = 0.001, 0.004, and 0.011, respectively, Kruskal-Wallis test). Interestingly, the 17.5 kDa protein was more abundant in five men with stage T1 prostate cancer than in eight with stage T2 (P = 0.016, two tailed Mann-Whitney U-test corrected for ties). CONCLUSIONS: These proteins, particularly the 15.9 kDa one, may be used for the diagnosis or monitoring of prostate cancer and differentiation from BPH, and have the potential for antibody-based chip SELDI-TOF technology. Identified proteins may be targets for immunotherapy.

Biomarkers, Tumor↗

Serum insulin level, disease stage, prostate specific antigen (PSA) and Gleason score in prostate cancer.

In the present study, we assessed the relationship of serum insulin levels and three surrogate markers of recurrence, T stage, PSA, and Gleason score, in men with localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients were asymptomatic and had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum insulin levels were determined by chemoluminescent assay with a standard, commercially available instrument. Patients were divided into three previously defined risk groups: Low risk: PSA < or =10, stage < or =T2a, or Gleason grade < or =6. Medium risk: 10 7, tumour in seminal vesicle biopsy, PSA >15 or stage T2c or T3. One hundred and sixty-three men with prostate cancer were studied. There was a significant increase in serum insulin with risk group (P=0.003, one way anova). Tukey's multiple range test showed that the insulin levels of high risk patients were significantly higher than the insulin levels of medium and low risk patients (P=0.05) but the insulin levels of medium and low risk patients were not significantly different from one another. Multivariate linear regression, with insulin as the dependent variable, Gleason score, PSA, and T stage (T1, T2, T3) as the independent variables, was significant overall (P<0.001, r(2)=0.120). Increased T stage was independently correlated with increased serum insulin levels (P<0.001). Gleason score was negatively, insignificantly correlated with serum insulin level (P=0.059). The positive correlation of PSA and insulin level was not significant (P=0.097). To assure normal distribution of insulin and PSA values, the regression was repeated with log (insulin) as the dependent variable, log (PSA), T stage (T1, T2, T3), and Gleason score as independent variables. The regression was significant overall (P=0.002, r(2) =0.095). Increased T stage was independently correlated with increased log (insulin level) (P=0.026). Gleason score was negatively, insignificantly correlated with log (insulin) level (P=0.728). The positive correlation of log (PSA) and log (insulin) levels was significant (P=0.010). The relationship between increased insulin level and advanced tumour stage in prostate cancer we describe here is biologically quite plausible, since insulin is a growth factor. Further studies may document whether serum insulin levels might be a useful biomarker of prostate cancer stage.

Aged↗

Association between serum triiodothyronine (t3) level and risk of disease recurrence in men with localized prostate cancer.

We assessed the relationship of serum triiodothyronine (t3) level and risk of disease recurrence in men treated for localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients had been initially diagnosed on the basis of rising prostate specific antigen (PSA) or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum (t3) level was determined by chemoluminescent assay with a standard, commercially available instrument (Immulite Diagnostic Products Corporation, Los Angeles, California). Sixty-eight men with prostate cancer were studied. In our treatment protocol, patients are divided into three risk groups: low risk: serum PSA</=10, stage</=T2a, or Gleason grade</=6. These patients are treated with a radioactive implant; moderate risk: serum PSA 10-15 or Gleason 7 or stage</=T2b. These patients are treated with 3 months of combined hormonal therapy followed by an implant; high risk: Gleason >7, tumor in seminal vesicle biopsy, serum PSA >15 or stage T2c or T3. These patients are treated with 3 months combined hormonal therapy, an implant, and after 2 months break 6000 rad external beam radiotherapy. There was a significant increase in serum t3 with risk category (P=0.011). Tukey's multiple range B-test showed a significant difference between the t3 levels of the high risk patients, when compared to the t3 levels of the moderate (P=0.013) and low risk patients (P=0.041). The range test showed no significant difference between the t3 levels of the moderate and low risk patients (P=0.897). Because t3 levels may be affected by age, we performed multivariate linear regression, with t3 as the dependent variable. There was a statistically significant (P=0.035) association of t3 level with risk group, but there was no significant association of t3 with age (P=0.803). Multivariate linear regression, with t3 as dependent variable, PSA, Gleason score, and stage as independent variables showed a significant overall association of the three independent variables with t3 (P=0.042), though individually the relationships were not significant. None of the men had a t3 level that was above the normal range for our laboratory (137 ng/dl). Urologists are actively seeking additional biomarkers of prostate cancer aggressiveness. Many prostate cancers are quite indolent and may never cause a problem, but it is impossible to identify such tumors with certainty. Further studies of serum t3 level as a biomarker in prostate cancer might therefore be worthwhile. With more and better biomarkers, many older men might be spared the rigors of radiation therapy and/or surgery and the complications. Also, new prostate cancer therapies might be directed toward inhibiting the mitogenic effects of t3.Prostate Cancer and Prostatic Diseases (2001) 4, 232-234.

Journal Article↗

Body mass, age, and the APC I1307K allele in Ashkenazi Jewish prostate cancer patients.

The I1307K mutation of the adenopolyposis coli gene (APC), located on chromosome 5q21-q22, is associated with an increased risk of cancer in Ashkenazi Jews. In the present study, we analyzed age and body mass of Ashkenazi Jewish prostate cancer patients, with and without the APC I1307K mutation. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. A familial history was obtained by interview or self-report questionnaire. Histological confirmation of diagnosis was obtained for all subjects. The I1307K allele of the APC gene was detected by amplification of lymphocyte DNA from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. We studied 135 Ashkenazi Jewish men with prostate cancer. The youngest was 49, the oldest 80, average age 68 +/- 6.88 (mean +/- SD). The older patients carrying the wild type APC allele tended to have a lower body mass than the younger ones (r = -.27, P =.002). Of 71 patients under 70 years old, 65 carried the wild type APC allele, and had a body mass index of 28. 7 +/- 4.23 kg/m(2). The six men under age 70 carrying the I1307K APC allele had a body mass index of 26.87 +/- 1.44 kg/m(2). The difference in body mass index of the two groups is significant (P =. 032, t test for unequal variance). Increased body mass is a prostate cancer risk factor, and hereditary prostate cancer is associated with younger patients. Therefore, our finding, that patients under age 70 carrying the I1307K allele are significantly thinner than those carrying the wild type allele, suggests that the APC I1307K allele is also a prostate cancer risk factor. Our results are in accord with other studies indicating that APC mutations increase the risk of prostate cancer.

Age Factors↗

Absence of 185delAG mutation of the BRCA1 gene and 6174delT mutation of the BRCA2 gene in Ashkenazi Jewish men with prostate cancer.

Epidemiological studies have demonstrated a clustering of breast and prostate cancers in some families. Moreover, there is an increase in the number of cases of prostate cancer in families with inherited mutations of the breast cancer susceptibility gene BRCA1. We assessed the role of BRCA1 and BRCA2 in prostate cancer. We tested for the BRCA1 185delAG frameshift mutation, found in 0.9% of Ashkenazi Jews, and the BRCA2 6174delT mutation, found in 1% of Ashkenazi Jews, in Ashkenazi Jewish men with prostate cancer. We studied 60 Ashkenazi men with prostate cancer. A family history was obtained by interview or a self-report questionnaire. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. Mutations of BRCA1 and BRCA2 were detected by amplification of lymphocyte DNA from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Patients' ages ranged from 55 to 80 years (mean +/- s.d. 70 +/- 5.25). There were six men with a family history of prostate cancer; three of these had a father with prostate cancer. Five of the men had a family history of breast cancer, in a mother, a sister or an aunt. None of the men had a family history of both breast and prostate cancer. None of the 60 men carried the 185delAG BRCA1 or 6174delT BRCA2 mutations. Of 268 Ashkenazi Jewish women with sporadic breast cancer, tested in an unrelated study, 16 carried either the 185delAG mutation of BRCA1 or the 6174delT mutation of BRCA2. There was a significant difference in the incidence of the BRCA1 and BRCA2 mutations in the breast and prostate cancer cases (P = 0.05, two-tailed Fisher's exact test). The contribution of germline BRCA1 and BRCA2 mutations to prostate cancer incidence is probably small and could be limited to specific subgroups.

Aged↗

Detection of snow-crab antigens by air sampling of a snow-crab production plant.

BACKGROUND AND OBJECTIVE: We previously assessed the prevalence of occupational asthma (OA) to snow-crab in production plant workers. We also showed that this type of OA is related to immediate immunological reactivity as demonstrated by skin reactivity and increased specific IgE antibodies. However, we did not show that snow-crab antigens causing immunological reactivity and OA could be found in the air sampling in the plants atmosphere. This was the purpose of the current work. MATERIAL AND METHODS: Area air samples worn by workers at four different worksites of a snow-crab producing plant were obtained on PVC filters with an SKC pump run at 1.5 L/min for 2 h. Snow-crab was being boiled and processed during the air sampling periods. Filters were analysed by RAST inhibition in a blind manner (i.e. without knowledge of the worksite where the filter originated). RESULTS: Eluate from one of the four sites (#2) had the highest protein concentration and yielded the highest per cent inhibition of RAST--13% inhibition with the snow-crab meat, 23% and 28% inhibition with the snow crab water RAST in two separate assays. An eluate taken from a filter at another site (#1) showed borderline reactivity (1% and 10% inhibition in two assays) whereas the two other ones and a control filter were negative. The two filters that contained snow-crab proteins were the ones nearest the boiling process, site #2 being the nearest followed by site #1. It was estimated that a 28% inhibition corresponded to approximately 8.6 micrograms of proteins and to approximately 1.5 micrograms of allergens on the filter. CONCLUSION: This study suggests that airborne snow-crab-derived proteins, released during the boiling process, are the cause of immunological reactivity and of OA to snow-crab.

Air Pollutants, Occupational↗

Reverse transcriptase-polymerase chain reaction for prostate-specific antigen may be a prognostic indicator in breast cancer.

Among women with node-negative breast cancer and small tumours, it is important to identify those with tumours that will recur, so that they may receive adjuvant therapy, while sparing those with tumours that will not recur the hazards of adjuvant treatment. A reverse transcriptase-polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) may be used to identify circulating metastatic cells in patients with prostate cancer. Approximately 30% of breast cancer cells also produce PSA. Therefore, we tested the PSA RT-PCR assay on blood specimens from women with breast cancer. We evaluated 78 women at Mount Sinai Medical Center with histologically confirmed breast cancer. Venous blood (5 cm3) from the women was collected in ethylene diaminetetraacetic acid (EDTA)-treated collection tubes and approximately 400 ng of RNA from each sample was subjected to an RT-PCR. We were able to detect the amplified PSA fragment in 18 of 78 women with breast cancer; 7 of the 18 women with the PSA fragment had localised, small, node-negative tumours, both oestrogen receptor (ER) positive and ER negative. We could not detect the amplified PSA fragment in 20 normal women and 22 normal men. We conclude that PSA RT-PCR may be a useful method for determining the presence of circulating metastatic cells in some women with node-negative breast cancer, and therefore the potential for these women to develop recurrent disease and thus benefit from adjuvant therapy.

Adult↗

Allergy to cockroaches in patients with asthma and rhinitis in an urban area (Madrid).

Previous studies have established that cockroach allergens are important sensitizing agents in the induction of rhinitis and asthma principally in urban areas. This study was undertaken to assess skin test reactivity and specific IgE antibody reactivity to extracts of Periplaneta americana (P.a.), Blattella germanica (B.g.), B. orientalis (B.o.), and a fecal extract of B. germanica (FEB.g.) in a group of patients with rhinitis and asthma living in an urban area in Europe. We examined clinical characteristics and aerollergen sensitivities of 171 consecutive Madrid urban patients with rhinitis and asthma who met the criteria for the study. A comprehensive clinical evaluation was followed by skin prick test with common allergens and saline extracts of P.a., B.g., B.o., and FEB.g. and measurement of serum specific IgE antibody to cockroach extracts. The age of patients ranged from 7 to 68 years (mean 20.4 +/- 16). A total of 153 (90.5%) subjects were atopic and 19 (10%) were considered nonallergic. Pollen sensitivity (66.5%) was most prevalent, distantly followed by sensitivity to cockroach (25.7%), mite (20%), cat (15.5%), Alternaria alternata (14.5%), dog (14%), and food (2%). Skin test reactivity to cockroach extracts was 37 (21.6%) to B.o., 20 (11.6%) to P.a., 19 (11.1%) to B.g. and five (2.9%) to FEB.g. Twenty-one of these patients had rhinitis, 19 rhinitis and asthma, and one only asthma; 26 had perennial symptoms, while 16 had seasonal (spring) symptoms; three (1.7%) patients had only positive prick test to cockroach; all had perennial rhinitis and/or asthma. Eighteen (10.5%) patients had specific serum IgE (RAST 1 or 2) to B.o., 13 (7.6%) to P.a., and six (3.5%) to B.g. Eighty (46.7%) patients had visual evidence of cockroach infestation in their home, mostly B.o.; 31 had positive prick test to cockroach (P < 0.0003). The results indicate that sensitivity to outdoor allergens (pollen) is more prevalent than to indoor allergens. Cockroach sensitization is the most important indoor allergen in our area, and B.o. accounts for most cockroach sensitization.

Adolescent↗

Nomograms for determining the probability of axillary node involvement in women with breast cancer.

We have previously reported that a history of pregnancy is independently associated with axillary node involvement in breast cancer patients. We have now studied additional women with breast cancer and have used our data and the logistic model to produce nomograms for determining the risk of axillary node involvement, based on tumor size, age, and number of pregnancies. There was an increase in the incidence of axillary node involvement in women with a history of pregnancy. To exclude the confounding effect that tumor size or age might have on node involvement, logistic regression was performed. Pregnancy, tumor size, and age were the three independent variables. History of pregnancy had a significant effect on node involvement (P = 0.036) that was independent of tumor size and age. Nomograms were constructed from these data. Surgeons do not perform an axillary dissection in every breast cancer patient. If the axilla is clinically negative and the tumor small, the surgeon, medical oncologist, and radiation oncologist may decide that a dissection need not be done. The nomograms in this article may allow for a more methodical choice of patients for axillary dissection. Moreover, a radiation oncologist might use the nomograms to help decide whether to irradiate an undissected axilla.

Adult↗