Coexpression of IGF-1R and c-Src proteins in human pancreatic ductal adenocarcinoma.

Aberrant c-Src protein kinase activation has been identified as one of the molecular alterations involved in human pancreatic carcinogenesis. It has been postulated that c-Src may induce transformation by causing the overexpression of the insulinlike growth factor-1 receptor (IGF-1R) in pancreatic tumor cell lines. To further study the interaction between c-Src and IGF-1R proteins in human pancreatic cancer, we examined their coexpression in 47 human pancreatic ductal adenocarcinomas (PDA).

Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas.

The insulin-like growth factor-1 receptor (IGF1-R) is a cellular receptor overexpressed in many tumor cell lines and in some human tumors that seems to play a critical role in transformation, tumorigenicity, and metastasis. To date, a comprehensive evaluation of tissue distribution of IGF1-R in human carcinomas from different anatomical sites has been lacking. Using stage-oriented human cancer tissue microarrays, we studied IGF1-R expression and distribution in a group of 152 human carcinomas from a variety of anatomical sites and from 63 normal tissues through immunohistochemistry.

Multilineage gene expression in human bone marrow stromal cells as evidenced by single-cell microarray analysis.

The nonhematopoietic stromal cells of the bone marrow are critical for the development of hematopoietic stem cells into functionally competent blood cells. This study addresses the question of whether bone marrow stromal cell cultures in the Dexter system propagate multiple different mesenchymal stromal cell types or one stromal cell type that expresses multiple phenotypes. Results show that isolated single stromal cells simultaneously express transcripts associated with osteoblast, fibroblast, muscle, and adipocyte differentiation.

Overexpression of interleukin-2 receptor alpha in a human squamous cell carcinoma of the head and neck cell line is associated with increased proliferation, drug resistance, and transforming ability.

It has been previously demonstrated that human carcinomas express interleukin-2 receptor (IL-2R) alpha, beta, and gamma chains. The beta and gamma chains of IL-2R have intermediate binding affinity for IL-2 and are responsible for the intracellular signaling cascades after IL-2 stimulation. IL-2Ralpha lacks the cytoplasmic domain, but is essential for increasing the IL-2-binding affinity of other receptors.

Insulin-like growth factor 1 receptor activates c-SRC and modifies transformation and motility of colon cancer in vitro.

Colorectal carcinomas have been found to express increased levels of IGF1 and IGF1-R, as compared to normal or adenomatous colonic mucosa, and it has been postulated that a subset of colorectal cancers are under the autocrine regulation of the IGF1/IGF1-R system. In this study, we selected human colorectal carcinoma cell lines with high (SW620, HT29, L4A) and low (CaCo2, and HCT 116) expression of IGF1-R by flow cytometry. Compared to the IGF1-R(-) cells, the IGF1-R(+) cells revealed a more aggressive phenotype as demonstrated by a higher proliferation rate (approximately 2-fold increase) in response to IGF1, higher degree of transformation (approximately 5-to-15-fold increase in colony formation in soft agar), increased resistance to serum deprivation-induced apoptosis [1-7 apoptotic cells/5 microscopic fields, as compared to 37 to 101 apoptotic cells/5 microscopic fields of the IGF1-R(-) cells], and higher migratory capability measured by a wounding assay [IGF1-R(+) cells migrated a distance of up to 15 millimeters from the cut edge of the monolayer, while the IGF1-R(-) cells were able to migrate only 2-3 millimeters away from the same reference point].

Identification of NY-ESO-1, MAGE-1, and MAGE-3 in head and neck squamous cell carcinoma.

Background: Certain tumor antigens have been identified that stimulate an immune response, thus making them targets for immunotherapy. NY-ESO-1, MAGE-1, and MAGE-3 are such antigens. This study was undertaken to determine their presence or absence in head and neck squamous cell cancers and to correlate this with patient characteristics.

Appraising the economic efficiency of cancer treatment: an exploratory analysis of lung cancer.

This paper tests whether the measured cost-effectiveness of treating different subgroups of an incident population of lung cancer patients differs significantly and, by implication, whether the provision of care to these patients is tolerably efficient in economic terms. Data from administrative records and Registry follow-up on 544 non-small cell lung cancer patients diagnosed at a single NCI-designated Comprehensive Cancer Center are used to conduct the empirical analysis. The main results show statistically significant differences in cumulative costs and patient outcomes across subgroups differing by disease stage and treatment modality.

Treatment of stage IIIA non-small cell lung cancer.

Stage IIIA non-small cell lung cancer represents a relatively heterogeneous group of patients with metastatic disease to the ipsilateral mediastinal (N2) lymph nodes and also includes T3N1 patients. Presentations of disease range from apparently resectable tumors with occult microscopic nodal metastases to unresectable, bulky multistation nodal disease. Controversy abounds as to the optimal treatment of the various stage IIIA subsets, which is fueled by a lack of meaningful, large randomized trials.

Screening strategies for the identification of multiple antibody-positive relatives of individuals with type 1 diabetes.

The objective of this study was to determine the extent to which different screening strategies could identify a population of nondiabetic relatives of a proband with type 1 diabetes who had two or more immunologic markers from the group consisting of islet cell antibodies (ICA), micro insulin autoantibodies (MIAA), GAD65 autoantibodies (GAA), and ICA512 autoantibodies (ICA512AA). Relatives of subjects with type 1 diabetes were screened for ICA as part of the Diabetes Prevention Trial-Type 1. A total of 71,148 samples were also tested for GAA and ICA512AA.

An improved method of region grouping for microcalcification detection in digital mammograms.

A very important issue, namely region grouping, in computer-assisted diagnostic detection of microcalcification clusters (MCC) in digital mammograms is addressed in this work. In the diagnosis of breast cancer, MCC, instead of single and isolated microcalcifications, are considered clinically significant. Grouping individual regions segmented from digital mammograms, therefore, should be a component in an automatic MCC detection system.

Synthetic analogs of green tea polyphenols as proteasome inhibitors.

Background: Animal, epidemiological and clinical studies have demonstrated the anti-tumor activity of pharmacological proteasome inhibitors and the cancer-preventive effects of green tea consumption. Previously, one of our laboratories reported that natural ester bond-containing green tea polyphenols (GTPs), such as (-)-epigallocatechin-3-gallate [(-)-EGCG] and (-)-gallocatechin-3-gallate [(-)-GCG], are potent and specific proteasome inhibitors. Another of our groups, for the first time, was able to enantioselectively synthesize (-)-EGCG as well as other analogs of this natural GTP.

Indirect economic effects of long-term breast cancer survival.

Purpose: The indirect morbidity/disability costs of breast cancer may be rising as a consequence of the growth in the population of long-term survivors. This study was conducted to test whether women who have survived breast cancer for at least 5 years experience long-lasting or continuing economic consequences that are attributable to their disease.

Description Of Study: A group of 105 women who initially had been treated for breast cancer approximately 5 years before were interviewed to obtain data on economic, demographic, and health changes in the period since diagnosis.

Functional impairment and the economic consequences of female breast cancer.

Recent trends in breast cancer diagnosis and mortality suggest that long-term survivors are now more likely to be functionally impaired and, hence, more likely to experience adverse economic outcomes. This study tests whether women who have survived breast cancer for at least five years exhibit more, or more severe, functional impairments than otherwise similar women without breast cancer. It also tests whether women with more severe impairments experience poorer economic outcomes attributable to their functional status.

Irinotecan and gemcitabine in patients with solid tumors: phase I trial.

Using a day 1 and 8, every-3-week schedule, our purpose was to determine the maximum tolerated dose of irinotecan (CPT-11, Camptosar) that can be administered immediately after gemcitabine (Gemzar) at a dose of 1,000 mg/m2 IV. In this phase I trial, the maximum tolerated dose was defined as the dose level immediately below the level in which two of the first three patients in any cohort, or at least two of six patients in any expanded cohort, experienced dose-limiting toxicity. Dose-limiting toxicity pertained only to toxicity during the first cycle of treatment.

A novel beta-lactam antibiotic activates tumor cell apoptotic program by inducing DNA damage.

Many of the anticancer drugs in current use are toxic and thus limited in their efficacy. It therefore becomes essential to develop novel chemotherapeutic agents with lower levels of toxicity. The beta-lactam antibiotics have been used for many years to treat bacterial infections with limited or no toxicity.

Inhibition of Rho GTPases with protein prenyltransferase inhibitors prevents leukocyte recruitment to the central nervous system and attenuates clinical signs of disease in an animal model of multiple sclerosis.

The ICAM-1-mediated brain endothelial cell (EC)-signaling pathway induced by adherent lymphocytes is a central element in facilitating lymphocyte migration through the tight endothelial barrier of the brain. Rho proteins, which must undergo posttranslational prenylation to be functionally active, have been shown to be an essential component of this signaling cascade. In this study, we have evaluated the effect of inhibiting protein prenylation in brain ECs on their ability to support T lymphocyte migration.

Phase II trial of topotecan and cisplatin in persistent or recurrent squamous and nonsquamous carcinomas of the cervix.

Objective: Cisplatin is a standard treatment in advanced, recurrent cervical cancer. Because topotecan is an established treatment in gynecologic malignancies such as ovarian cancer and exhibits nonoverlapping toxicity with cisplatin, a phase II trial was conducted to evaluate the tolerability and antitumor activity of a cisplatin/topotecan doublet in persistent or recurrent cervical cancer patients.

Methods: Patients with bidimensionally measurable persistent or recurrent squamous cell and non squamous cell cervical cancer and adequate bone marrow were enrolled.

The evolution and application of toxicity criteria.

The assessment and reporting of toxicity plays a central role in oncology. The foundation of toxicity reporting is the toxicity criteria system. Multiple systems have been developed and have evolved substantially since first introduced more than 20 years ago.

Cancer and folie à deux: case report, treatment, and implications.

Purpose: This report describes the uncommon psychopathological state best known as folie à deux, or shared psychotic disorder, in a unique case in which the grandiose, religious delusions of a woman with uterine cancer are shared with her husband.

Overview: More than 50% of patients with cancer meet the criteria for diagnosis of major psychiatric disorders. Certainly, these disorders may occur as a result of the stress of the cancer diagnosis and treatment, but also because of a predisposition to psychiatric illness or a pre-existing psychiatric illness.

A simple method to improve probe set estimates from oligonucleotide arrays.

A popular commercially available oligonucleotide microarray technology employs sets of 25 base pair oligonucleotide probes for measurement of gene expression levels. A mathematical algorithm is required to compute an estimate of gene expression from the multiple probes. Previously proposed methods for summarizing gene expression data have either been substantially ad hoc or have relied on model assumptions that may be easily violated.

Validity and reliability of the FACT-G scale for use in the older person with cancer.

This project was designed to evaluate the Functional Assessment of Cancer Therapy General Scale (FACT-G) for use in the older patient with cancer. Subjects were administered the MOS Short Form Health Survey (SF-36) and the FACT-G scale. Subscale and total scores were compared using the Pearson product correlation test.

Utility of internal mammary lymph node removal when noted by intraoperative gamma probe detection.

Background: Lymphatic mapping (LM) for breast cancer has made internal mammary node (IMN) detection practical and dependable. This study demonstrates the necessity of IMN removal when suggested by intraoperative radioguided surgery detection.

Methods: From April 1998 to July 2000, 1273 patients underwent LM for breast cancer.

Digital mammography: wavelet transform and Kalman-filtering neural network in mass segmentation and detection.

Rationale And Objectives: The authors developed a new adaptive module to improve their computer-assisted diagnostic (CAD) method for mass segmentation and classification. The goal was an adaptive module that used a novel four-channel wavelet transform with neural network rather than a two-channel wavelet transform with manual subimage selection. The four-channel wavelet transform is used for image decomposition and reconstruction, and a novel Kalman-filtering neural network is used for adaptive subimage selection.

Clinical relevance of internal mammary node mapping as a guide to radiation therapy.

Background: The surgical management of breast cancer has changed markedly with the development of lymphatic mapping and sentinel lymph node (SLN) biopsy. Lymphatic mapping technique varies with respect to injection method, mapping agent, and surgical technique. The decision to pursue the internal mammary nodes (IMN) is another source of controversy.