Strengthening cancer biology research, prevention, and control while reducing cancer disparities: student perceptions of a collaborative master's degree program in cancer biology, preventions, and control.

This article provides the findings of a survey of previous and current students in the UDC/GU-LCCC master's degree program. This master's degree program, Cancer Biology, Prevention, and Control is administered and taught jointly by faculty of a Minority Serving Institution, the University of the District of Columbia, and the Lombardi Comprehensive Cancer Center to incorporate the strengths of a community-based school with a research intensive medical center. The program was initiated in 2008 through agreements with both University administrations and funding from the National Cancer Institute. The master's degree program is 36 credits with a focus on coursework in biostatistics, epidemiology, tumor biology, cancer prevention, medical ethics, and cancer outreach program design. For two semesters during the second year, students work full-time with a faculty person on a laboratory or outreach project that is a requirement for graduation. Students are supported and encouraged to transition to a doctoral degree after they obtain the master's and many of them are currently in doctorate programs. Since the inception of the program, 45 students have initiated the course of study, 28 have completed the program, and 13 are currently enrolled in the program. The survey was designed to track the students in their current activities, as well as determine which courses, program enhancements, and research experiences were the least and most useful, and to discern students' perceptions of knowledge acquired on various aspects of Cancer Biology Prevention, and Control Master's Program. Thirty of the 35 individuals to whom email requests were sent responded to the survey, for a response rate of 85.7%. The results of this study will inform the strengthening of the Cancer Biology program by the Education Advisory Committee. They can also be used in the development of comparable collaborative master's degree programs designed to address the significant disparities in prevalence of cancer, low screening awareness, and access to and outcomes of cancer prevention and treatment services. This, in turn, will contribute to the elimination of the dearth of underrepresented minority scientists who address these disparities. By far, the students were satisfied with the program and believe that it has had significant impact on their ability to contribute to cancer prevention and control. They provided both general and specific recommendations to strengthen the program.

The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells.

Syk is a protein tyrosine kinase that is widely expressed in haematopoietic cells. It is involved in coupling activated immunoreceptors to downstream signalling events that mediate diverse cellular responses including proliferation, differentiation and phagocytosis. Syk expression has been reported in cell lines of epithelial origin, but its function in these cells remains unknown. Here we show that Syk is commonly expressed in normal human breast tissue, benign breast lesions and low-tumorigenic breast cancer cell lines. Syk messenger RNA and protein, however, are low or undetectable in invasive breast carcinoma tissue and cell lines. Transfection of wild-type Syk into a Syk-negative breast cancer cell line markedly inhibited its tumour growth and metastasis formation in athymic mice. Conversely, overexpression of a kinase-deficient Syk in a Syk-positive breast cancer cell line significantly increased its tumour incidence and growth. Suppression of tumour growth by the reintroduction of Syk appeared to be the result of aberrant mitosis and cytokinesis. We propose that Syk is a potent modulator of epithelial cell growth and a potential tumour suppressor in human breast carcinomas.

Detection of chromosomal aberrations by a whole-genome microsatellite screen.

Chromosomal aberrations are a common cause of multiple anomaly syndromes that include developmental and growth retardation. Current microscopic techniques are useful for the detection of such aberrations but have a limit of resolution that is above the threshold for phenotypic effect. We hypothesized that a genomewide microsatellite screen could detect chromosomal aberrations that were not detected by standard cytogenetic techniques in a portion of these individuals. To test this hypothesis, we performed a genomewide microsatellite screen of patients, by use of a currently available genetic-marker panel that was originally designed for meiotic mapping of Mendelian traits. We genotyped approximately 400 markers on 17 pairs of parents and their children who had normal karyotypes. By using this approach, we detected and confirmed two cases of segmental aneusomy among 11 children with multiple congenital anomalies. These data demonstrate that a genomewide microsatellite scan can be used to detect chromosomal aberrations that are not detected by microscopic techniques.

De novo mosaic add(3) characterized to be trisomy 14q31-qter using spectral karyotyping and subtelomeric probes.

We describe a 19-year-old patient with a de novo mosaic add(3) chromosome (extra material of unknown origin on the 3q). The use of spectral karyotyping and fluorescence in situ hybridization using subtelomeric probes permitted the full characterization of the cytogenetic abnormality. The additional material on 3q was found to originate from 14q31-qter. This is one of the few reported cases with trisomy 14q31-qter and is the first mosaic case.

Prenatal diagnosis of partial trisomy through in situ hybridization on amniocytes with whole chromosome and centromere-specific DNA probes. A case report.

BACKGROUND: DNA probes specific for whole chromosomes or portions of chromosomes can provide important information to aid the clinician in managing pregnancy and the geneticist in relaying accurate recurrence risk information to the patient. CASE: In this case, sonography was ordered because of a low fundal height in a 29-year-old primigravida at 35 weeks' gestational age; it revealed major fetal anomalies. A small supernumerary marker was seen in some cultured amniocytes. Metaphase spreads were analyzed by means of fluorescence in situ hybridization using a centromere probe specific for chromosome 22 and a whole chromosome probe for the 11 chromosome. In situ hybridization showed that the marker chromosome was a derivative of chromosome 22 with 11q material attached near the centromere. The fetal karyotype was 47,XY,+der(22) t(11;22)(q23.3;q11.2)mat. The mother was later found to be a balanced translocation carrier. CONCLUSION: It was possible to offer rapid prenatal diagnosis for this family using interphase analysis with the 22 centromere probe. The patient had chorionic villus sampling, and DNA probes were used to analyze cells directly from the biopsy. The signal representing the supernumerary marker was not observed. Karyotype analysis later showed that the fetus was normal but a translocation carrier. This report illustrates that rapid in situ hybridization can provide important information in known cases of translocation carriers.

Prenatal diagnosis of tetrasomy 12p by in situ hybridization: varying levels of mosaicism in different fetal tissues.

Prenatal diagnosis of tetrasomy 12p is complicated by the discrimination of the 12p isochromosome from the duplication 21q as well as the level of mosaicism demonstrated in the particular tissue sampled. In this disease, a high percentage of chromosomally abnormal cells are generally found in fibroblastic cells, but lymphocyte karyotypes from the same individual may be normal. We report on the pregnancy of a 37-year-old female who presented to our centre at 16 weeks' gestation for genetic amniocentesis. Sonography of the fetus revealed dextrocardia and diaphragmatic hernia. Chromosome analysis of amniocytes demonstrated mosaicism of a 47,XY,+i(12p) line in 80 per cent of cells and a normal male line (20 per cent), consistent with the Pallister-Killian syndrome. Following termination, a 220 g male fetus of 18 weeks was examined. A flattened nose and low-set ears were noted. In situ hybridization with a chromosome 12 centromeric probe in lymphocytes and skin cells unequivocally confirmed the karyotype and showed the presence of a single centromere in the abnormal chromosome, suggesting a true isochromosome. Chromosome analysis of various fetal tissues was performed and the following percentages of abnormal cells were found: skin 100 per cent, chorion 50 per cent, placenta 30 per cent, and blood 80 per cent. The high frequency of tetrasomic cells in fetal blood at this early gestational age is noteworthy, since most reports of this syndrome show a very low percentage of abnormal cells postnatally.

Effect of calcium-modifying drugs on mouse in vitro fertilization and preimplantation development.

Calcium ions are required for normal in vitro fertilization and preimplantation development in the mouse. This study examined the effects of alterations in Ca2+ flux and distribution on sperm penetration of eggs and embryo cleavage. Compounds used included diltiazem, a Ca2+ channel blocker, and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), an antagonist of intracellular calcium release. Incubation of sperm and eggs with diltiazem at 30 and 10 microM and TMB-8 at 30, 10, and 3 microM resulted in depressed fertilization compared with controls. Motility was not inhibited at these concentrations of either drug. Both drugs also depressed progression of mouse embryos from 2-cell to blastocyst at 30 and 3-microM concentrations. This study suggests that both Ca2+ flux and distribution to specific cellular sites are required for normal mouse in vitro fertilization and early preimplantation development.