The American College of Radiology and the American Brachytherapy Society practice parameter for the performance of low-dose-rate brachytherapy.

Brachytherapy is the use of radionuclides to treat malignancies or benign conditions by means of a radiation source placed close to or into the tumor or treatment site. This practice parameter refers only to the use of radionuclide brachytherapy. Brachytherapy alone or combined with external beam therapy plays an important role in the management and treatment of patients with cancer.

Diagnosis and management of an isolated pediatric plexiform neurofibroma involving the hepatic and celiac plexus using multimodality approach: problem solving with diffusion-weighted magnetic resonance imaging.

Plexiform neurofibroma with involvement of the gastrointestinal tract is a very rare entity in children. Here, we present a rather unique case of a 9-year-old boy with no clinical signs or features of neurofibromatosis type 1. A periportal mass lesion was incidentally found after performing an ultrasound in this previously healthy child.

Methylation-specific PCR.

Methylation-specific PCR is a rapid method used to determine the methylation status of DNA. Not only does methylation affect the expression of genes in normal cells, but it is now known that disease processes such as cancer can result in abnormal DNA methylation patterns. Methylation-specific PCR can be used to investigate imprinted genes, to assess human tumors for clonality by studying genes inactivated on the X chromosome, and to examine abnormally methylated CpG islands in neoplasia.

Dose intensity for breast cancer: where do we go from here?

Strategies utilizing high-dose chemotherapy for treatment of breast cancer have been the subject of significant controversy over the past decade. Disappointing results from randomized phase III trials in metastatic and high-risk, early stage breast cancer have tempered enthusiasm for this approach. A significant problem with large, randomized phase III trials is that improvements in therapy and supportive care cannot be rapidly incorporated into treatment, and the question under study may quickly become obsolete.

Evasion of early cellular response mechanisms following low level radiation-induced DNA damage.

DNA damage that is not repaired with high fidelity can lead to chromosomal aberrations or mitotic cell death. To date, it is unclear what factors control the ultimate fate of a cell receiving low levels of DNA damage (i.e.

Post-mastectomy radiation in male breast cancer.

Background And Purpose: Previous studies of male breast cancer have suggested that due to the lack of breast tissue, post-mastectomy radiation should be routinely utilized in all stages of this disease. We propose that the pattern of local recurrence in male breast cancer is, stage for stage, similar to female breast cancer and, therefore, the indications for post-mastectomy radiation should be similar.

Materials And Methods: We conducted a retrospective analysis of 44 cases of male breast cancer from 1967 to 1995.

Chemotherapy and bone marrow reserve: lessons learned from autologous stem cell transplantation.

Cytotoxic chemotherapy is often complicated by hematopoietic toxicity. The degree of aplasia and the rapidity of count recovery following chemotherapy are indicative of bone marrow reserve. Patients who generally have a normal bone marrow function will recover from chemotherapy-induced cytopenia relatively rapidly.

Hypermethylation-associated Inactivation of the Cellular Retinol-Binding-Protein 1 Gene in Human Cancer.

The effects of retinol (vitamin A) depend on its transport and binding to nuclear receptors. The cellular retinol-binding protein 1 (CRBP1) and the retinoic acid receptor beta2 (RARbeta2) are key components of this process. Loss of CRBP1 expression occurs in breast tumors, but the mechanism is not known.

Growth status significantly affects the response of human lung cancer cells to antitumor polyamine-analogue exposure.

Human solid tumors frequently have a relatively small growth fraction,which interferes with the action of many chemotherapeutic agents that target actively cycling cells. Several polyamine analogues are currently being developed for clinical application against human solid tumors including N1,N11-bis(ethyl)norspermine. Therefore, an effort was made to examine the effects of growth rate on polyamine-analogue efficacy.

AML1 stimulates G1 to S progression via its transactivation domain.

Inhibition of AML1-mediated transactivation potently slows G1 to S cell cycle progression. In Ba/F3 cells, activation of exogenous AML1 (RUNX1)-ER with 4-hydroxytamoxifen prevents inhibition of G1 progression mediated by CBFbeta-SMMHC, a CBF oncoprotein. We expressed three AML1-ER variants with CBFbeta-SMMHC in Ba/F3 cells.

Early operable breast cancer.

Early operable breast cancer is a potentially curable disease. However, a substantial number of patients are at risk for systemic recurrence and death. Breast conservation therapy (BCT) should be considered the preferred surgical option for most women with early operable breast cancer.

Atrasentan, an endothelin-receptor antagonist for refractory adenocarcinomas: safety and pharmacokinetics.

Purpose: Endothelin receptors, particularly the ET(A) receptor, have been shown to participate in the pathophysiology of prostate and other cancers. Atrasentan, an endothelin antagonist, binds selectively to the ET(A) receptor. This study evaluated the safety, pharmacokinetics, and maximum-tolerated dose of atrasentan in cancer patients.

CD34 selection using three immunoselection devices: comparison of T-cell depleted allografts.

Background: T-cell depletion of allografts markedly reduces the incidence of GvHD following BMT. The approach taken at our Center has utilized the physical separation method of counterflow centrifugal elutriation (CCE), augmented by recovery of stem cells from lymphocyte-rich fractions by immunoaffinity selection of CD34(+) stem cells. We wanted to compare the performance characteristics of three commercially available selection devices, as well as the clinical outcomes of patients who received allografts engineered by the different devices.

Long-term follow-up of intensive ara-C-based chemotherapy followed by bone marrow transplantation for adult acute lymphoblastic leukemia: impact of induction Ara-C dose and post-remission therapy.

We report single institution outcome of brief, intensive ara-C-based chemotherapy using bone marrow transplantation as primary intensification for untreated adult patients with acute lymphoblastic leukemia (ALL). Overall disease-free and overall survival were inferior to those reported with prolonged chemotherapy modeled on pediatric protocols. Survival and disease-free survival were superior for patients receiving allogeneic BMT compared with chemopurged autologous transplant or maintenance chemotherapy (patients ineligible for or declining BMT).

Chromosome segregation and cancer: cutting through the mystery.

Mitosis is the most dramatic--and potentially dangerous--event in the cell cycle, as sister chromatids are irreversibly segregated to daughter cells. Defects in the checkpoints that normally maintain the fidelity of this process can lead to chromosomal instability (CIN) and cancer. However, CIN--a driving force of tumorigenesis--could be the cancer cell's ultimate vulnerability.

Phase I study of N(1),N(11)-diethylnorspermine in patients with non-small cell lung cancer.

Purpose: Polyamines are essential for tumor growth; consequently, agents that interfere with their metabolisms have been developed as antineoplastic agents. Diethylnorspermine (DENSPM) is one such agent. A focused Phase I clinical trial in patients with advanced non-small cell lung cancer was undertaken.

Use of SERMs for the adjuvant therapy of early-stage breast cancer.

Tamoxifen was the first in a class of drugs now commonly referred to as selective estrogen receptor modulators or SERMs. SERMs exhibit tissue-specific estrogenic agonist/antagonist activity through their ability to bind to the estrogen receptor alpha (ER) protein and interact with coregulatory proteins, thereby modulating transcription of estrogen target genes. Since its first approval by the United States Food and Drug Administration (FDA) in 1977, tamoxifen has been found to (a) lower the risk of recurrence and death for women with early-stage hormone receptor-positive breast cancer, irrespective of menopausal and node status or use of adjuvant chemotherapy; (b) reduce the risk of invasive breast cancer following breast conservation in women with ductal carcinoma in situ (DCIS); and (c) reduce the risk of breast cancer in high-risk women.

Hypermethylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma.

Background: The gene encoding the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is transcriptionally silenced by promoter hypermethylation in several human cancers, including diffuse large B-cell lymphoma (B-DLCL). MGMT promoter hypermethylation is a favorable prognostic marker in patients with brain tumors treated with alkylating agents.

Methods: In a retrospective cohort study, we used methylation-specific polymerase chain reaction to analyze the MGMT promoter methylation status in tumor DNA of B-DLCL patients receiving cyclophosphamide as part of multidrug regimens.

A cyclooxygenase-2 (COX-2) inhibitor compared with dexamethasone in a survival study of rats with intracerebral 9L gliosarcomas.

Although dexamethasone is very effective for controlling peritumoral cerebral edema, it is associated with distressing side effects that decrease the quality of life for many patients. One potential mechanism to explain the ability of dexamethasone to repair blood-brain barrier dysfunction is through the inhibition of cyclooxygenase-2 (COX-2). The purpose of this study was to determine in a rat brain tumor model whether SC-236, a selective COX-2 inhibitor, is as effective as dexamethasone.

DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis.

Cancer cells have aberrant patterns of DNA methylation including hypermethylation of gene promoter CpG islands and global demethylation of the genome. Genes that cause familial cancer, as well as other genes, can be silenced by promoter hypermethylation in sporadic tumors, but the methylation of these genes in tumors from kindreds with inherited cancer syndromes has not been well characterized. Here, we examine CpG island methylation of 10 genes (hMLH1, BRCA1, APC, LKB1, CDH1, p16(INK4a), p14(ARF), MGMT, GSTP1 and RARbeta2) and 5-methylcytosine DNA content, in inherited (n = 342) and non-inherited (n = 215) breast and colorectal cancers.

Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours.

Cancer is an epigenetic disease at the same level that it can be considered a genetic disease. In fact, epigenetic changes, particularly DNA methylation, are susceptible to change and are excellent candidates to explain how certain environmental factors may increase the risk of cancer. The delicate organization of methylation and chromatin states that regulates the normal cellular homeostasis of gene expression patterns becomes unrecognizable in the cancer cell.

Evolving therapies: farnesyltransferase inhibitors.

Farnesyltransferase inhibitors (FTIs) are compounds designed to interfere with the signal transduction of cancer cells containing ras gene mutations. Specifically, FTIs were designed to prevent the farnesylation of Ras and other intracellular proteins, and they have been shown to have an effect on malignant cell proliferation and survival. However, the actual intracellular target of FTIs and the cellular determinants of drug action that correlate with antitumor effects currently are unknown.