Biomedical subjects

Kenneth J Pienta

Publications and source records attributed to Kenneth J Pienta.

80 records · Page 5Linked to original sources

PubMedDate not supplied

MIM, a potential metastasis suppressor gene in bladder cancer.

Using a modified version of the mRNA differential display technique, five human bladder cancer cell lines from low grade to metastatic were analyzed to identify differences in gene expression. A 316-bp cDNA (C11-300) was isolated that was not expressed in the metastatic cell line TccSuP. Sequence analysis revealed that this gene was identical to KIAA 0429, has a 5.3-kb transcript that mapped to 8q24.1. The protein is predicted to be 356 amino acids in size and has an actin-binding WH2 domain. Northern blot revealed expression in multiple normal tissues, but none in a metastatic breast cancer cell line (SKBR3) or in metastatic prostatic cancer cell lines (LNCaP, PC3). We have named this gene Missing in Metastasis (MIM) and our data suggest that it may be involved in cytoskeletal organization.

Amino Acid Sequence↗

PubMedDate not supplied

Suppression of tumor recurrence and metastasis by a combination of the PHSCN sequence and the antiangiogenic compound tetrathiomolybdate in prostate carcinoma.

Plasma fibronectin-mediated invasion of human DU145 prostate cancer cell line was efficaciously inhibited in a rat tumor model by treatment with Ac-PHSCN-NH(2) peptide. Invasion of DU145 cells was stimulated by the PHSRN sequence of plasma fibronectin. However, PHSCN acts as a competitive inhibitor of PHSRN-mediated invasion. In the current study, we determined whether PHSCN could inhibit the recurrence and metastasis of DU145 tumors after excision of the primary tumor in an athymic nude mouse model. We demonstrated that mice treated thrice weekly with intravenous Ac-PHSCN-NH(2) peptide survived tumor-free for more than 30 weeks post-primary tumor excision, whereas their untreated counterparts succumbed to recurrence and/or metastatic disease in significantly less time. Because of the universal requirement for angiogenesis in solid tumor growth, we tested the efficacy of copper deficiency induced by tetrathiomolybdate (TM) to retard tumor growth in the Dunning prostate cancer model. Significant reduction in size of the primary tumor was observed in mice rendered copper deficient. We sought to reduce tumor growth at the primary and metastatic sites by combining the anti-invasion Ac-PHSCN-NH(2) peptide with TM. Improved survival, fewer metastatic lesions, and excellent tolerability were observed with the combination therapy.

Adenocarcinoma↗

PubMedDate not supplied

Detection and isolation of circulating tumor cells in urologic cancers: a review.

The American Cancer Society has estimated that in 2003, there will be approximately 239,600 new cases of urologic cancer diagnosed and 54,600 urologic cancer-related deaths in the United States. To date, the majority of research and therapy design have focused on the microenvironment of the primary tumor site, as well as the microenvironment of the metastatic or secondary (target) tumor site. Little attention has been placed on the interactions of the circulating tumor cells and the microenvironment of the circulation (i.e., the third microenvironment). The purpose of this review is to present the methods for the detection and isolation of circulating tumor cells and to discuss the importance of circulating tumor cells in the biology and treatment of urologic cancers.

Cell Survival↗

PubMedDate not supplied

The current state of hormonal therapy for prostate cancer.

Androgen deprivation therapy remains a mainstay of treatment for men with prostate cancer. New uses for hormonal therapy, including use in the adjuvant and neoadjuvant setting, are being evaluated. Prevention of the side effects of therapy has led to the development of alternative schedules and therapeutics.

Androgen Antagonists↗

PubMedDate not supplied

Advances in prostate cancer chemotherapy: a new era begins.

Prostate cancer continues to be the most common lethal malignancy diagnosed in American men and the second leading cause of male cancer mortality. Over 60 years ago, Huggins and Hodges discovered androgen deprivation as a first-line therapy for metastatic prostate cancer, which leads to remissions typically lasting 2 to 3 years, but in most men prostate cancer ultimately progresses to an androgen-independent state resulting in death due to widespread metastases. Multiple mechanisms of androgen independence have now been documented, including amplification of the androgen receptor as well as signal transduction pathways that bypass the androgen receptor completely. In 2004, two landmark studies demonstrated a survival advantage in androgen-independent prostate cancer patients utilizing docetaxel chemotherapy, setting a new standard of care for this disease. In addition, treatments with the bisphosphonate zoledronic acid and systemic radioisotopes have also been shown to have palliative benefits in this population. Building on these advances, several new traditional chemotherapeutic agents as well as new targeted therapies are under development.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

In vivo visualization of metastatic prostate cancer and quantitation of disease progression in immunocompromised mice.

While survival periods for patients with localized prostate cancer have increased, there is still no curative therapy for metastatic disease. Using non-invasive bioluminescent imaging, we designed a comprehensive murine model to monitor tumor location and expansion. We detected micrometastases after one week that correlated by gross necropsy, autoradiography, and histopathology with organ and skeletal lesions seen clinically. We calculated in vivo kinetics for tumor growth based on biophoton emissions and observed significantly faster growth of bone lesions and of overall tumor burden in young mice compared to old mice. This model provides a controllable biological system for further investigation into the pathogenesis of metastatic prostate cancer and evaluation of new therapies.

Animals↗

PubMedDate not supplied

Proptosis and decreased vision secondary to prostate cancer orbital wall metastasis.

The case of a 66-year-old gentleman who presented with unilateral proptosis, eye pain and partial loss of vision seven years after his original prostate cancer diagnosis is reported. MRI of the orbits revealed a 2-cm lesion in the posterolateral right orbital wall near the optic foramen with compression of the optic nerve. Metastatic orbital lesions are relatively uncommon in prostate cancer. Treatment is palliative and varies according to the time of presentation in the course of the disease. This patient's symptoms resolved after reinitiation of combined androgen blockade.

Aged↗

PubMedDate not supplied

Prostate cancer presenting as visual changes.

Dural metastases have traditionally been considered a rare complication of prostate cancer; various case reports and autopsy series from the past have shown rates between 1 and 9%. Recent data from our advanced prostate cancer autopsy series, however, demonstrate a rate of dural lesions around 25%, suggesting that such complications may be more prevalent than previously reported. A case of prostate cancer, which was diagnosed after the patient presented with visual changes, is reported. Subsequent work-up revealed a lesion in the left tentorium, which was determined to be adenocarcinoma and stained positive for PSA and PAP.

Adenocarcinoma↗