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J Stec

Publications and source records attributed to J Stec.

At least 19 recordsLinked to original sources
PubMed2006

Bortezomib (VELCADE) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits.

BACKGROUND: Bortezomib (VELCADE) is a potent inhibitor of the 26S proteasome with broad antitumor activity. We performed a phase II study of bortezomib to evaluate its clinical effects in patients with metastatic breast cancer. PATIENTS AND METHODS: Twelve patients with metastatic breast cancer were treated with bortezomib (VELCADE) at a dosage of 1.5 mg/m(2) administered biweekly for 2 weeks with 1 week of rest in a 21-day cycle. The primary objective was clinical response rate. Toxicity and pharmacodynamics data were also obtained. RESULTS: No objective responses were observed. One patient had stable disease, and 11 others experienced disease progression. The median survival time was 4.3 months (range, 0.9-37 months). The most common grade 3 or 4 toxicities included fatigue (58%; n = 7) and skin rash (33%; n = 4). The mean inhibition of specific chymotryptic activity was 53.1% (+/- 13.33%). A statistically significant reduction in the plasma interleukin-6 level was seen (P = 0.0354). CONCLUSION: Bortezomib was well tolerated but showed limited clinical activity against metastatic breast cancer when used as a single agent. The future development of this agent for the treatment of breast cancer should be guided by in vivo models that optimize activity in combination with other antitumor agents.

Adult↗
PubMed2005

A single-gene biomarker identifies breast cancers associated with immature cell type and short duration of prior breastfeeding.

The pathogenesis of breast cancers that do not express estrogen receptors or Her-2/neu receptors (ER-/HER2- phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABA(A)) receptor subunit pi (GABApi, GABRP) in some breast cancers with ER-/HER2- phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide microarrays. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure GABApi gene expression in a separate cohort of 121 invasive breast cancers. GABApi gene expression values from TxP and RT-PCR were standardized and compared with clinicopathologic characteristics in the 203 patients. GABApi gene expression was increased in 16% of breast cancers (13/82 TxP, 20/ 121 RT-PCR), particularly in breast cancers with ER-/HER2- phenotype (60%), and breast cancers with basal-like genomic profile (60%). The profile of genes coexpressed with GABApi in these tumors was consistent with an immature cell type. In multivariate linear regression analysis, the level of GABApi gene expression was associated with ER-/HER2- phenotype (P < 0.0001), younger age at diagnosis (P = 0.0003), and shorter lifetime duration of breastfeeding (< or = 6 months) in all women (P = 0.017) and specifically in parous women (P = 0.013). GABApi gene expression was also associated with combinations of high grade with ER-/HER2- phenotype (P = 0.002), and with Hispanic ethnicity (P = 0.036). GABApi gene expression is increased in breast cancers of immature (undifferentiated) cell type and is significantly associated with shorter lifetime history of breastfeeding and with high-grade breast cancer in Hispanic women.

Biomarkers, Tumor↗
PubMed2004

Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.

PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P <or=.09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. CONCLUSION: Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.

Adult↗
PubMed2001

Single- vs. multiple-set strength training in women.

The aim of this study was to compare the effects of single-set and multiple-set strength training in women. Twenty-seven women (aged 20-40 years) with basic experience in strength training were randomly allocated to either a single-set group (n = 9), a 3-set group (n = 9), or a nontraining control group (n = 9). Both training groups underwent a whole-body strengthening program, exercising 2 days a week for 6 weeks. Exercises included bilateral leg extension, bilateral leg curl, abdominal crunch, seated hip adduction/abduction, seated bench press, and lateral pull-down. The single-set group's program consisted of only 1 set of 6-9 repetitions until failure, whereas the multiple-set group trained with 3 sets of 6-9 repetitions until failure (rest interval between sets, 2 minutes). Two times before and 3 days after termination of the training program, subjects were tested for their 1 repetition maximum strength on the bilateral leg extension and the seated bench press machine. Data were analyzed using a repeated-measures analysis of variance, Scheffé tests, t-tests, and calculation of effect sizes. Both training groups made significant strength improvements in leg extension (multiple-set group, 15%; single-set group, 6%; p 0.05). However, in the seated bench press only the 3-set group showed a significant increase in maximal strength (10%). Calculation of effect sizes and percentage gains revealed higher strength gains in the multiple-set group. No significant differences were found in the control group. These findings suggest superior strength gains occurred following 3-set strength training compared with single-set strength training in women with basic experience in resistance training.

Adult↗
PubMed1992

Inhibition of DNA synthesis and decreased reproductive capacity in cattle maintained on semi-arid rangeland with Acacia species as a major component of available browse.

The ability of bovine lymphocytes to initiate in vitro blastogenesis in response to mitogen stimulation or to initiate DNA excision repair after treatment with a mutagen was evaluated as a function of the differing environmental conditions under which donor animals were maintained. Crossbred Brahman-Hereford F1 females were held on either a humid, coastal bermudagrass, improved pasture at Overton, TX, or in low or high grazing pressure herds on a semi-arid rangeland (Acacia-dominated shrubland) at Uvalde, Tx. Peripheral blood lymphocytes (PBL) from these animals were examined to determine their in vitro ability to engage in phytohemagglutinin (PHA)-stimulated blastogenesis and to initiate excision repair of DNA damage after exposure of the cells to the model polynuclear hydrocarbon carcinogen 7,8-dihydrodiol-9, 10-epoxy-benzo(a) pyrene (BPDE). PBL from cattle at both locations were compared, with significantly decreased blastogenesis and DNA excision repair observed in PBL from Uvalde high grazing pressure cattle. Cattle in the Uvalde high grazing pressure herd also exhibited significantly decreased reproductive efficiency. The data indicate that ingestion of sufficient quantities of palatable, but toxic, forage species available at the Uvalde test site is sufficient to decrease DNA synthesis associated with either mitogen-stimulated blastogenesis or DNA excision repair in bovine PBL, and suggest that the reduction in PBL DNA synthesis may be correlated with the changed reproductive efficiency in animals ingesting an increased ratio of forage from Acacia species.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1990

Zinc and copper metabolism in nephrotic syndrome.

The effect of proteinuria on urinary zinc and copper excretion was studied in children with nephrotic syndrome (NS). Clearance, fractional excretion, and urinary excretion of zinc and copper were significantly higher in children with relapse of NS than in the same children with remission of NS or in healthy children. A linear correlation was found between proteinuria and urinary zinc and copper excretion in relapse of NS. The results of this study suggest that zinc and copper deficiency in NS may be related also to increased urinary zinc and copper losses.

Adolescent↗
PubMed1990

[Is mass ambulatory health care of the population realistic under the present conditions?].

Mass (complete) dispensarization of the population is the highest type of individual care of the population not only in disease but also in health. Extension of dispensary care to the entire population is consistent with the implementation of primary health care (WHO, UNICEF--Alma Ata 1978) and can be achieved by the year 2000 also under our conditions, provided certain organizational, personal and professional prerequisites are met. The latter do not depend only on the health services but have an overall community character.

Czechoslovakia↗
PubMed1989

Purification of Norman Murine Sarcoma DNA polymerase alpha forms with different DNA template primer binding affinity and different specific activity.

1. DNA polymerase alpha was isolated from Norman Murine Myxosarcoma cells using ion exchange, immunoaffinity, and DNA affinity chromatography, showing two distinct enzyme forms designated A1 and A2. 2. Chromatographic analysis of polymerase alpha forms A1 and A2 indicate a charge difference and a difference in affinity of binding to DNA between polymerase alpha forms which were equally reactive to anti-DNA polymerase alpha monoclonal IgG. 3. Polymerase A1 specific activity was about 3600 U/mg while A2 specific activity was about 40,000 U/mg.

Animals↗
PubMed1989

[Renal excretion of zinc in children with kidney diseases].

The authors investigated the renal zinc excretion in 33 children with chronic glomerulonephritis, in 30 children with tubulo-interstitial nephritis, 12 children with nephrotic syndrome and 31 children with isolated haematuria. In all groups the Zn clearance was slightly raised, as compared with the control group. The Zn clearance was highly significantly elevated in nephrotic syndrome. The authors correlated the urinary finding (proteinuria, haematuria, leucocyturia) with Zn clearance. Children with a positive urinary finding had a higher Zn clearance than those with a negative finding. There was a close correlation between selective proteinuria and Zn clearance in children with nephrotic syndrome.

Child↗
PubMed1988

Activation of a low specific activity form of DNA polymerase alpha by inositol-1,4-bisphosphate.

A low activity form of DNA polymerase alpha immunoaffinity-purified from adult-derived human fibroblasts was activated by interaction with phosphatidylinositol-4-monophosphate, while a high activity form of the enzyme did not interact with phosphatidylinositol-4-monophosphate or its derivatives. Phosphatidylinositol-4-monophosphate was apparently hydrolyzed in the presence of a highly purified low activity form of DNA polymerase alpha, effecting the release of diacylglycerol and the retention of inositol-1,4-bisphosphate by the enzyme complex. The resulting inositol-1,4-bisphosphate/protein complex exhibited increased affinity of binding to DNA template/primer and increased deoxynucleotidyltransferase activity. These data indicate that inositol-1,4-bisphosphate may function as an effector molecule in the activation of a low activity form of human DNA polymerase alpha and suggest that it may function as a second messenger during the initiation of mitosis in stimulated cells.

1-Phosphatidylinositol 4-Kinase↗
PubMed1988

DNA polymerase alpha activity in mitogen-activated lymphocytes.

DNA polymerase alpha isolated from adult-derived lymphocytes was separated into isozyme forms with low (A1) and high (A2) specific activity. In quiescent lymphocytes only A1 was detected, while mitogen-stimulated lymphocytes contained both A1 and A2 enzyme. Polymerase alpha A1, but not A2, interacted with phosphatidylinositol, ATP, and phosphatidylinositol kinase to yield an activated enzyme with increased affinity of binding to DNA. Mitogen-stimulated lymphocytes showed increased enzyme protein and total activity for both A1 and A2, but, when pre-treated with cycloheximide, exhibited an apparent increase in A2 specific activity with no increase in activity for A1 polymerase. These data suggest that mitogen stimulation of lymphocytes increased total DNA polymerase alpha activity by the phosphoinositide-related activation of polymerase alpha A1 to an A2-like form and by initiating de-novo synthesis of polymerase alpha A2.

Adult↗
PubMed1987

Lability of DNA polymerase alpha correlated with decreased DNA synthesis and increased age in human cells.

DNA excision repair and mitogen-initiated blastogenesis in human cells declined in efficiency as an apparent function of decreased DNA polymerase alpha specific activity with increased age of the cell donor. DNA polymerase alpha isolated from fetal cells contained a single, high-specific-activity enzyme form that could not be further activated and that was stable with regard to enzyme activity and affinity for DNA template-primer. DNA polymerase alpha isolated from adult-derived cells contained both low-specific-activity and high-specific-activity forms. The low-activity enzyme form, which showed low affinity of binding to DNA template-primer, was activated by treatment with phosphatidylinositol, 32P-ATP, and phosphatidylinositol kinase, resulting in a 32P-labeled enzyme that exhibited high affinity of binding to DNA template-primer. The activated enzyme was unstable, exhibiting a loss of 32P-label correlated with the loss of both specific activity and high affinity of binding to DNA template-primer. The data suggest that DNA polymerase alpha isolated from adult-derived human cells has low-activity and high-activity forms. Decreased specific activity of DNA polymerase alpha correlated with increased age of the donor appears to be a function of loss of an enzyme activator molecule resulting in diminished ability of the enzyme to bind DNA template-primer.

Adult↗