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Biomedical subjects

K J Pienta

Publications and source records attributed to K J Pienta.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effect of age and race on the survival of men with prostate cancer in the Metropolitan Detroit tricounty area, 1973 to 1987.

OBJECTIVES: Reports have demonstrated that African Americans diagnosed with prostate cancer have a poor survival compared with whites. We examined the impact of age, race, and stage of disease on survival for men diagnosed with prostate cancer. METHODS: A retrospective analysis was made of men diagnosed with prostate cancer utilizing the Surveillance, Epidemiology, and End Results Program (SEER) database. A total of 12,907 men (9339 white, 3568 black) diagnosed from January 1, 1973 through December 31, 1987 were included in the study. For each stage of disease, survival experience was examined using Kaplan-Meier and life table methods, followed by analysis using Cox's proportional hazard model. RESULTS: African-American men have a poorer survival than whites for all stages of prostate cancer when the cancer is diagnosed at younger ages. These differences in survival were not demonstrated for men diagnosed with prostate cancer after age 70. CONCLUSIONS: Age and race should be taken into account when assessing the survival of patients with prostate cancer.

Adenocarcinoma↗
PubMed1995

4-Hydroxyphenylretinamide in the chemoprevention of cancer.

It has been suggested that ultimately half of all cancers might be prevented by early interventions (Costa, 1993). 4HPR has been shown to be an effective and safe agent in various in vivo animal trials and well tolerated in human trials. At present multiple clinical trials are assessing its efficacy in preventing a variety of cancers.

Chemoprevention↗
PubMed1994

Oral etoposide in the treatment of hormone-refractory prostate cancer.

BACKGROUND: Hormone-refractory prostate cancer generally remains a chemotherapy-resistant tumor and therefore warrants the continued evaluation of promising agents. METHODS: Twenty-two eligible patients with hormone-refractory prostate cancer were treated with oral etoposide at a dosage of 50 mg/m2/day for 21 days in a 28-day cycle. Response was evaluated using standard solid tumor response criteria. RESULTS: There were two partial responses of 6 and 14 months' duration, respectively. Two patients had disease stabilization, one for 6 months and one for 12 months. Median survival was 31 weeks, with an overall 1-year survival of 30%. Reversible alopecia and myelosuppression were the primary toxicities noted. CONCLUSIONS: Single-agent oral etoposide has minimal activity in patients with hormone-refractory prostate cancer.

Adenocarcinoma↗
PubMed1994

Coupling of cell structure to cell metabolism and function.

The fact that cells make directed decisions regarding how to use energy, i.e., where to direct intracellular particles or where to move, suggests that energy can be, and is, harnessed in specific ways. It is now well established that the chemical reactions of the cell do not occur in nonorganized soup, but rather in the context of ordered structure. The physical components that make up this ordered structure of the cell are part of the tissue matrix, which consists of the dynamic linkages between the skeletal networks of the nucleus (the nuclear matrix), the cytoplasm (the cytoskeleton), and the extracellular environment (the extracellular matrix). To understand gene function and how the energy of the cell is directed towards accomplishing the tasks directed by DNA (gene expression), a further understanding of how cell structure is tied to cellular energy and function is required. We propose that the structural components of the cell harness cellular energy to direct cell functions by providing a dynamic bridge between thermodynamics and gene expression.

Animals↗
PubMed1994

Alterations in cellular gene expression without changes in nuclear matrix protein content.

Cell metabolism and function are modulated in part by cell and nuclear shape. Nuclear shape is controlled by the nuclear matrix, the RNA-protein skeleton of the nucleus, and its interactions with cytoskeletal systems such as intermediate filaments and actin microfilaments. The nuclear matrix plays an important role in cell function and gene expression because active genes are bound to the nuclear matrix whereas inactive genes are not. It is unknown, however, how genes move on and off the matrix, and whether these events require compositional protein changes, i.e., alterations in protein content of the nuclear matrix, or other, more subtle alterations and/or modifications. The purpose of this investigation was to begin to determine how nuclear matrix protein composition is related to gene expression. We demonstrate that gene expression can change without apparent changes in the protein composition of the nuclear matrix in MCF10A breast epithelial cells.

Actins↗
PubMed1994

Review of the role of androgenic hormones in the epidemiology of benign prostatic hyperplasia and prostate cancer.

OBJECTIVE: Examine current knowledge and concepts on the role of androgenic hormones in the epidemiology of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: Review of the clinical and scientific literature on normal androgen physiology, hormonal physiology of BPH and PCa tissue, serum hormone levels in patients with BPH or PCa, and the correlation between serum and tissue androgenic hormones. RESULTS: BPH and PCa are enormous clinical problems for our health care system; profound changes in the clinical aspects of these diseases are evident in recent years. Early identification or prevention are realistic goals; identification of higher risk groups would be extremely valuable. Androgen stimulation of the prostate is likely to be important in the promotion of BPH or PCa. Tissue hormone measurements have not identified substantial differences in hormone levels, but precise pathologic control of the tissue examined is suspect. Examinations of serum hormone levels in disease states have produced conflicting results, but the presence or absence of BPH or PCa was often based on imprecise clinical observations, making interpretation difficult. There are minimal data confirming that the serum hormones measured previously actually reflect intraprostatic tissue activity. CONCLUSIONS: The value of serum hormone measurements to identify higher risk groups for BPH or PCa is an area of continuing uncertainty because of substantial flaws in the design of many previous studies based on a failure both to define the presence or absence of BPH or PCa precisely in patients studied and measure the appropriate androgen metabolites. Similarly, it is not possible reliably to implicate differences in androgenic stimulation as a cause for racial differences in PCa. The ability of serum hormone levels to correlate with prostatic tissue androgenic stimulation has not been evaluated. Additional research in the relationships between androgenic stimulation and the development of clinically significant BPH or PCa is needed.

Androgens↗
PubMed1994

An unstable nuclear matrix may contribute to genetic instability.

Cancer cells proliferate and metastasize against the body's defense mechanisms due to their ability to change in response to challenges, both from the body's internal defenses as well as those from external sources, such as radiation and chemotherapy. This ability of tumor cell populations to change and grow in response to these stresses as well as to hold populations of cells with diverse abilities has been termed 'tumor cell heterogeneity'. Tumor cell heterogeneity is thought to arise in cancer cell populations as a result of genetic instability, an undefined process by which the genetic material of the cell is rendered more labile and more likely to undergo changes in structure, conformation, and function. DNA is structurally and functionally organized by the nuclear matrix, the dynamic RNA-protein skeleton of the nucleus. We provide here a proposal that provides a framework for understanding genetic instability in terms of an unstable nuclear matrix.

Animals↗
PubMed1994

Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate.

PURPOSE: Estramustine and etoposide (VP-16) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models. This led us to evaluate the effectiveness of this combination in the treatment of patients with metastatic prostate carcinoma refractory to hormone therapy. PATIENTS AND METHODS: Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d, were administered orally in divided doses for 21 days. Patients were then taken off therapy for 7 days and the cycle then repeated. Therapy continued until evidence of disease progression. RESULTS: Forty-two patients have been enrolled onto this trial with a minimum of 40 weeks follow-up. Of 18 patients with measurable soft tissue disease, three demonstrated a complete response (CR) and six a partial response (PR) for longer than 2 months. Of these 18 patients, pretreatment prostate-specific antigen (PSA) levels decreased by at least 75% in five men (28%) and by at least 50% in nine (50%). The median survival duration has not been reached in those patients who demonstrated a response either by soft tissue or PSA criteria. Of 24 patients with disease limited to bone, six (25%) demonstrated improvement and nine (38%) demonstrated stability in their bone scans. Five men (21%) demonstrated a decrease of at least 75% in pretreatment PSA levels and 14 (58%) demonstrated at least a 50% decrease; the median survival duration has not been reached in these patients. Pretreatment performance status is an important predictor of survival. CONCLUSION: We conclude that the combination of estramustine and VP-16 is an active oral regimen in hormone-refractory prostate cancer.

Adenocarcinoma↗
PubMed1993

A comparative study on expression of prostatic inhibin peptide, prostate acid phosphatase and prostate specific antigen in androgen independent human and rat prostate carcinoma cell lines.

Prostatic inhibin peptide (PIP), consisting of 94 amino-acid residues is synthesized and secreted by the prostate gland. Previous studies on immunohistochemical localization of PIP in primary prostatic tumor and their metastasis, have documented the value of this peptide as a tumor marker for diagnosis of prostate cancer (PCa). The present study was undertaken to compare the expression of PIP with that of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in androgen independent human PCa cell lines (PC-3, DU-145 and TSU-Prl) by immunoperoxidase technique. The results of the study indicated that the staining for PIP was more intense than that of PSA and PAP. The PSA staining was either weakly positive (PC-3) or totally absent (TSU-Prl and DU-145) while PAP staining was intense in PC-3 and moderate in the other two human cell lines. The intense staining observed for PIP in all of the androgen independent cell lines suggests that the synthesis and secretion of PIP is not primarily dependent on androgens. Furthermore, expression of these markers in Dunning rat cultured adenocarcinoma cell lines and tumors were studied. Positive staining for all three human tumor associated antigens (PIP, PSA and PAP) cross-reacting with the Dunning rat PCa cell lines and the tumors, suggest the suitability of this model for preclinical screening of various therapeutic agents.

Acid Phosphatase↗
PubMed1993

Nuclear matrix proteins in normal and breast cancer cells.

The progression from normal breast epithelium to a malignant phenotype may depend on changes in genetic events as well as failure of host mechanisms. Intermediate biomarkers are needed to more effectively identify malignant progression as well as to develop the potential for more specific treatments and prevention strategies. The nuclear matrix is the RNA-protein network which forms the skeleton of the nucleus and participates in DNA organization as well as multiple cellular functions. Nuclear matrix proteins have been demonstrated to be tissue and cell type specific as well as to reflect the state of cell differentiation and/or transformation. We prepared nuclear matrices from normal and cancer breast tissue from 10 patients with infiltrating ductal carcinoma of the breast as well as the MCF-10 mortal, immortal, and transfected breast cell lines. Nuclear matrices derived from normal human breast tissue and tumor tissue share common nuclear matrix proteins as well as demonstrate specific changes which appear to occur with the acquisition of the cancer phenotype. The MCF-10 cell lines demonstrate a phenotype that is intermediate between the normal and cancer tissue. These data suggest that the nuclear matrix may be an important biomarker in the pathogenesis of breast cancer.

Aged↗
PubMed1993

Risk factors for prostate cancer.

PURPOSE: To review the current state of knowledge regarding risk factors for prostate cancer. DATA SOURCES: Analysis of the literature through the use of MEDLINE as well as identification of papers through review of article bibliographies and the authors' personal files. Current data were also extracted from the Surveillance, Epidemiology, and End Results Program (SEER) database. DATA SELECTION: A review of risk factors for the development of prostate cancer. Emphasis was placed on identifying larger, controlled studies. DATA SYNTHESIS: The clinical incidence of prostate cancer is increasing. Risk factors for prostate cancer appear to include age, race, positive family history, vasectomy, and dietary fat intake. CONCLUSIONS: It appears that prostate cancer results from an interplay between endogenous hormones and environmental influences that include, most prominently, dietary fat.

Aged↗
PubMed1993

Treatment of prostate cancer in the rat with the synthetic retinoid fenretinide.

N-4-Hydroxyphenylretinamide (fenretinide or 4HPR), a derivative of retinoic acid, has been demonstrated to decrease the development of prostate cancer in a rat carcinogenesis model. This study was undertaken to determine if 4HPR is an effective agent for the treatment of established prostate cancer. In vitro, 4HPR was cytotoxic to rat and human prostate cancer cells as well as endothelial cells. Utilizing three different angiogenesis inhibition assays, it was demonstrated that 4HPR inhibited angiogenesis as well as endothelial cell motility and tubule formation. In vivo, 4HPR inhibited prostate cancer growth in a significant manner. These findings suggest that 4HPR may be a potent inhibitor of early prostate cancer growth.

Adenocarcinoma↗
PubMed1993

Effect of prostatic inhibin peptide (PIP) on prostate cancer cell growth in vitro and in vivo.

Prostatic inhibin peptide (PIP), is a 94 amino acid protein which is secreted by the prostate gland in an androgen-independent manner. Previously, it has been demonstrated that PIP appears to inhibit follicle-stimulating-hormone (FSH) secretion by the pituitary and prostate glands. In vitro, the Dunning R3327 rat prostate cancer cell line MAT-LyLu (MLL) cells and the human prostate cancer cell line PC-3, are stimulated to grow in response to exogenous FSH and these effects are blocked by PIP. In vivo, PIP inhibits the growth of the highly metastatic MLL prostate cancer cell line. A comparison of hormone levels in control and PIP-treated rats demonstrates a significant inhibition of FSH in treated animals. It appears that, in vivo, PIP may inhibit prostate cancer growth by inhibiting FSH. PIP may represent a novel hormonal treatment for prostate cancer.

Adenocarcinoma↗
PubMed1993

A common set of nuclear matrix proteins in prostate cancer cells.

The nuclear matrix is the RNA-protein network which forms the skeleton of the nucleus, and participates in DNA organization as well as in multiple cellular functions. Nuclear matrix proteins have been demonstrated to be tissue and cell type specific, as well as to reflect the state of cell differentiation and/or transformation. Previously, common nuclear matrix proteins were demonstrated between the rat prostate and the Dunning rat prostate adenocarcinoma cell lines. This study demonstrates that nuclear matrices derived from Dunning rat and human prostate cancer cell lines, as well as human tumors, share several common proteins. These common proteins suggest that alterations which occur in the nuclear matrix with prostate cell transformation may share a common basis.

Adenocarcinoma↗
PubMed1993

Inhibition of prostate cancer growth by estramustine and etoposide: evidence for interaction at the nuclear matrix.

Metastatic prostate cancer which is refractory to hormone therapy remains an incurable disease for which there is no effective therapy. We have begun to investigate the nuclear matrix, the RNA-protein network of the nucleus that plays an important role in DNA replication and gene expression, as a target for cancer chemotherapy. It was postulated that estramustine phosphate (EMP), an estradiol-nitrogen mustard conjugate that binds to the nuclear matrix, might enhance the cytotoxicity of etoposide (VP-16), a topoisomerase II inhibitor that acts at the level of the nuclear matrix. In a nascent DNA synthesis assay, EMP and etoposide interact to selectively inhibit new DNA synthesis on the nuclear matrix. In vitro, EMP and etoposide appeared to act synergistically to inhibit the growth of the metastatic Dunning rat prostate adenocarcinoma cell line Mat-LyLu as well as the metastatic human prostate adenocarcinoma cell line PC-3. In vivo, EMP and etoposide inhibited prostate adenocarcinoma growth in the Dunning Copenhagen rat model. These data have formed the basis of a Phase I/II clinical trial to examine the effect of EMP and etoposide in patients with stage D hormone-refractory prostate cancer.

Adenocarcinoma↗
PubMed1992

Nuclear morphometry for prediction of metastatic potential in early squamous cell carcinoma of the floor of the mouth.

Quantitative morphometric analyses of the nuclear shape have been successfully used with prostatic carcinoma to predict tumor metastatic potential and provide the most sensitive indicator of tumor aggressiveness in the individual case. We have studied the nuclear morphometric characteristics of 22 patients with T1 and T2 squamous cell carcinoma of the floor of the mouth to see if a correlation existed between lack of nuclear roundness and presence of cervical metastatic disease. A significant difference was identified between the morphology of cancer cell nuclei and normal squamous epithelium. Nuclear morphology could not be used to distinguish between patients with cervical node-negative and node-positive disease. Some patients both with and without cervical metastases who are long-term survivors had nuclear roundness scores in the highest range, reflecting greatest variation from normal.

Adult↗