The relationship of maternal low birthweight and infant low birthweight among African-American women at term delivery: Findings from the 1988 National Maternal and Infant Health Survey

A cohort study study design was used to study the relationship of maternal low birthweight and infant low birthweight among African American women delivering full term infants. The cohort consisted of 3,157 mother-infant pairs drawn from the 1988 National Maternal and Infant Health Survey conducted by the National Center for Health Statistics. The objectives of the study were (1) to determine if low birthweight, African American mothers delivering term infants experienced higher rates of infant low birthweight and (2) to examine the role of selected contributory variables in the relationship of maternal low birthweight and infant low birthweight. Contributory risk factors examined included maternal marital status, maternal age, maternal education, maternal height, maternal prepregnant weight, birth order, history of a prior low birthweight delivery, timing of prenatal care, number of prenatal visits, gestational length, infant gender, and behavioral factors of smoking, alcohol, and illicit drug use during pregnancy.^ Using logistic regression analysis, risk of infant low birthweight among maternal low birthweight mothers increased after controlling for less than a high school education, less than 20 years of age, prepregnant weight less than 100 lbs, history of a prior low birthweight delivery, birth order, smoking during pregnancy, and use of alcohol and illicit drugs during pregnancy, but was not statistically significant. Loss of statistical significance was attributed to a large reduction in cases available for analysis after including illicit drug use in the model.^ This study demonstrated a consistent pattern of increased rates of infant low birthweight among low birthweight mothers. The force of history remains, hence women with this trait should be carefully monitored and advised during pregnancy to decrease risk of a low birthweight infant, in order to decrease the chain of events leading to future generations of low birthweight mothers. ^

NANOPARTICLE AGGLOMERATES FOR PULMONARY DRUG DELIVERY

The Pulmonary route has been traditionally used to treat diseases of the respiratory tract. However, important research within the last two decades have shown that in addition to treating local diseases, a wide range of systemic diseases can be treated by delivering drugs to the lungs. The recent FDA approval to market Exubera, an inhalable form of insulin developed by Pfizer, to treat Diabetes, may just be the stepping stone that the pharmaceutical industry needs to market other drugs to treat systemic diseases via the lungs. However, this technology still needs repeated drug doses to control glucose levels, as the inhaled drug is cleared rapidly. Technologies have been developed where inhaled particles are capable of controlled release of drug from the lungs. An important feature of these technologies is the large geometric size of the particles that makes it difficult for the lung macrophages to clear these particles, which results in longer residence times for the particles in the lungs. Owing to the porosity, these particles have lower densities making them deliverable to the deep lungs. However, no modulation of drug release can be achieved with these technologies when more drug release may be required. This additional requirement can only be assuaged by additional dosing of the drug formulation, which can have undesirable effects due to excess loading of excipients in the lungs. In an attempt to bring about modulation of release from long residence time particles, a novel concept was developed in our laboratory that has been termed as the Agglomerated Vesicle Technology (AVT). Liposomes with encapsulated drug were agglomerated using well known cross linking chemistries to form agglomerates in the micron sized range. The large particles exhibited aerodynamic sizes in the respirable size range with minimal damage to the particles upon nebulization. By breaking the cross links between the liposomes with a cleaving agent, it was anticipated that triggered release of drug from the AVT particles could be achieved. In vivo studies done in healthy rabbits showed that post-administration modulation of drug release is possible from the AVT particles after the introduction of the cleaving agent. This study has important implications for the future development of this technology, where the AVT particles can be made “sensitive” to the product of disease. It is envisaged that a single dose of AVT containing the appropriate drug when administered to the lungs would maintain drug levels at a controlled rate over an extended period of time. When the need for more drug arises, the product of the disease would trigger the AVT particles to release more drug as needed to control the condition, thus eliminating the need for repeated drug doses and improved compliance amongst patients.

GuideView: structured multi-modal delivery of clinical guidelines.

GuideView is a system designed for structured, multi-modal delivery of clinical guidelines. Clinical instructions are presented simultaneously in voice, text, pictures or video or animations. Users navigate using mouse-clicks and voice commands. An evaluation study performed at a medical simulation laboratory found that voice and video instructions were rated highly.

Water-soluble fullerene (C60) derivatives as nonviral gene-delivery vectors.

A new class of water-soluble C60 transfecting agents has been prepared using Hirsch-Bingel chemistry and assessed for their ability to act as gene-delivery vectors in vitro. In an effort to elucidate the relationship between the hydrophobicity of the fullerene core, the hydrophilicity of the water-solubilizing groups, and the overall charge state of the C60 vectors in gene delivery and expression, several different C60 derivatives were synthesized to yield either positively charged, negatively charged, or neutral chemical functionalities under physiological conditions. These fullerene derivatives were then tested for their ability to transfect cells grown in culture with DNA carrying the green fluorescent protein (GFP) reporter gene. Statistically significant expression of GFP was observed for all forms of the C60 derivatives when used as DNA vectors and compared to the ability of naked DNA alone to transfect cells. However, efficient in vitro transfection was only achieved with the two positively charged C60 derivatives, namely, an octa-amino derivatized C60 and a dodeca-amino derivatized C60 vector. All C60 vectors showed an increase in toxicity in a dose-dependent manner. Increased levels of cellular toxicity were observed for positively charged C60 vectors relative to the negatively charged and neutral vectors. Structural analyses using dynamic light scattering and optical microscopy offered further insights into possible correlations between the various derivatized C60 compounds, the C60 vector/DNA complexes, their physical attributes (aggregation, charge) and their transfection efficiencies. Recently, similar Gd@C60-based compounds have demonstrated potential as advanced contrast agents for magnetic resonance imaging (MRI). Thus, the successful demonstration of intracellular DNA uptake, intracellular transport, and gene expression from DNA using C60 vectors suggests the possibility of developing analogous Gd@C60-based vectors to serve simultaneously as both therapeutic and diagnostic agents.

Targeted Multistage Delivery of Nanoparticles to the Bone Marrow

Bone marrow is a target organ site involved in multiple diseases including myeloproliferative disorders and hematologic malignancies and metastases from breast and prostate. Most of these diseases are characterized with poor quality of life, and the treatment options are only palliative due to lack of delivery mechanisms for systemically injected drugs which results in dose limitation to protect the healthy hematopoietic cells. Therefore, there is a critical need to develop effective therapeutic strategies that allow for selective delivery of therapeutic payload to the bone marrow. Nanotechnology-based drug delivery systems provide the opportunity to deliver drugs to the target tissue while decreasing exposure to normal tissues. E-selectin is constitutively expressed on the bone marrow vasculature, but almost absent in normal vessels, and therefore, E-selectin targeted drug delivery presents an ideal strategy for the delivery of therapeutic nanoparticles to the bone marrow. The objective of this study was to develop a novel bone marrow targeted multistage vector (MSV) via E-selectin for delivery of therapeutics and imaging agents. To achieve this goal, Firstly, an E-selectin thioaptamer (ESTA) ligand was identified through a two-step screening from a combinatorial thioaptamer library. Next, ESTA-conjugated MSV (ESTA-MSV) were developed and evaluated for their stability and binding to E-selectin expressing endothelial cells. Different types of nanoparticles including liposomes, quantum dots, and iron oxide nanoparticles were loaded into the porous structure of ESTA-MSV. In vivo targeting experiments demonstrated 8-fold higher accumulation of ESTA-MSV in the mouse bone marrow as compared to non-targeted MSV Furthermore, intravenous injection of liposomes loaded ESTA-MSV resulted in a significantly higher accumulation of liposome in the bone marrow space as compared to injection of non-targeted MSV or liposomes alone. Overall this study provides first evidence that E-selectin targeted multistage vector preferentially targets to bone marrow vasculature and delivers larger amounts of nanoparticles. This delivery strategy holds potential for the selective delivery of large amounts of therapeutic payload to the vascular niches in the bone marrow for the treatment of bone marrow associated diseases.

EVALUATION OF INTENSITY MODULATED RADIATION THERAPY (IMRT) DELIVERY ERROR DUE TO IMRT TREATMENT PLAN COMPLEXITY AND IMPROPERLY MATCHED DOSIMETRY DATA

Intensity modulated radiation therapy (IMRT) is a technique that delivers a highly conformal dose distribution to a target volume while attempting to maximally spare the surrounding normal tissues. IMRT is a common treatment modality used for treating head and neck (H&N) cancers, and the presence of many critical structures in this region requires accurate treatment delivery. The Radiological Physics Center (RPC) acts as both a remote and on-site quality assurance agency that credentials institutions participating in clinical trials. To date, about 30% of all IMRT participants have failed the RPC’s remote audit using the IMRT H&N phantom. The purpose of this project is to evaluate possible causes of H&N IMRT delivery errors observed by the RPC, specifically IMRT treatment plan complexity and the use of improper dosimetry data from machines that were thought to be matched but in reality were not. Eight H&N IMRT plans with a range of complexity defined by total MU (1460-3466), number of segments (54-225), and modulation complexity scores (MCS) (0.181-0.609) were created in Pinnacle v.8m. These plans were delivered to the RPC’s H&N phantom on a single Varian Clinac. One of the IMRT plans (1851 MU, 88 segments, and MCS=0.469) was equivalent to the median H&N plan from 130 previous RPC H&N phantom irradiations. This average IMRT plan was also delivered on four matched Varian Clinac machines and the dose distribution calculated using a different 6MV beam model. Radiochromic film and TLD within the phantom were used to analyze the dose profiles and absolute doses, respectively. The measured and calculated were compared to evaluate the dosimetric accuracy. All deliveries met the RPC acceptance criteria of ±7% absolute dose difference and 4 mm distance-to-agreement (DTA). Additionally, gamma index analysis was performed for all deliveries using a ±7%/4mm and ±5%/3mm criteria. Increasing the treatment plan complexity by varying the MU, number of segments, or varying the MCS resulted in no clear trend toward an increase in dosimetric error determined by the absolute dose difference, DTA, or gamma index. Varying the delivery machines as well as the beam model (use of a Clinac 6EX 6MV beam model vs. Clinac 21EX 6MV model), also did not show any clear trend towards an increased dosimetric error using the same criteria indicated above.

ECHOGENIC LIPOSOMES FOR NITRIC OXIDE DELIVERY AND BREAST CANCER TREATMENT

Liposomes, also known as nontoxic, biodegradable, and non-immunogenic therapeutic delivery vehicles, have been proposed as a carrier for drugs and antitumor agents in cancer chemotherapy. Echogenic liposomes (ELIP) have the potential to entrap air or bioactive gas to enhance acoustic reflectivity in ultrasound and are used as a contrast agent. The innovative part of this study is based on a novel concept to encapsulate nitric oxide (NO) gas into ELIP, deliver it to breast cancer cells, and control its release via direct ultrasound exposure. Studies on the effect of NO in tumor biology have shown that a high levels of NO (> 300 nM) leads to cytostasis or apoptosis by decreasing the translation of several cell cycle proteins and stimulating cancer cell death by activating the p53 pathway. The central hypothesis is that NO gas can be packaged and delivered through a delivery methodology to breast cancer cells to facilitate tumor regression with minimal systemic toxicity. The primary goal of this thesis is to develop an echogenic liposomal solution that has the ability to encapsulate NO, to release NO locally upon ultrasound exposure, and to induce breast cancer cell death. NO-containing echogenic liposomes (NO-ELIP) were prepared by the freezing-under-pressure method previously developed in our laboratory. It was necessary to evaluate stability of NO-ELIP and release of NO from NO-ELIP by measuring echogenicity using intravascular ultrasound images. Breast cancer cell lines, MDA-MB-231 and MDA-MB-468, were selected to investigate the cytotoxic effects of NO liberated from NO-ELIP and their response to NO concentration. Ultrasound-triggered NO release from NO-ELIP using ultrasound activation was studied. It was demonstrated that NO-ELIP remained stable for 5 hours in bovine serum albumin. Delivery of NO using NO-ELIP induced cytotoxicity and programmed cell death of MDA-MB-231 and MDA-MB-468 after 5 hours of incubation. Enhancement of the NO-ELIP effect for therapeutic application was observed with ultrasound activation. This work demonstrates that NO-ELIP can incorporate and deliver NO to breast cancer cells providing increased NO stability and ultrasound-controlled NO release. Improved therapeutic effect with the use of NO-ELIP is expected to be found for breast cancer treatment.

Anthropometric measures as a predictor of cephalopelvic disproportion

This study compared three body measurements, height, hip width (bitrochanteric) and foot length, in 120 Hispanic women who had their first birth by cesarean section (N = 60) or by spontaneous vaginal delivery (N = 60). The objective of the study was to see if there were differences in these measurements that could be useful in predicting cephalopelvic disproportion. Data were collected from two public hospitals in Houston Texas over a 10 month period from December 1994 to October 1995. The statistical technique used to evaluate the measures was discriminant analysis.^ Women who delivered by cesarean section were older, shorter, had shorter feet and delivered heavier infants. There were no differences in the bitrochanteric widths of the women or in the mean gestational age or Apgar scores of the infants.^ Significantly more of the mothers and infants were ill following cesarean section delivery. Maternal illness was usually infection; infant illness was primarily infection or respiratory difficulties.^ Discriminant analysis is a technique which allows for classification and prediction to which group a particular entity will belong given a certain set of variables. Using discriminant analysis, with a probability of cesarean section 50 percent, the best combination to classify who would have a cesarean section was height and hip width, correctly classifying 74.2 percent of those who needed surgery. When the probability of cesarean section was 10 percent and probability of vaginal delivery was 90 percent, the best predictor of who would need operative delivery was height, hip width and age, correctly classifying 56.2 percent. In the population from which the study participants were selected the incidence of cephalopelvic disproportion was low, approximately 1 percent.^ With the technologic assistance available in most of the developed world, it is likely that the further pursuit of different measures and their use would not be of much benefit in attempting to predict and diagnose disproportion. However, in areas of the world where much of obstetrics is "hands on", the availability of technology extremely limited, and the incidence of disproportion larger, the use of anthropometric measures might be useful and of some potential benefit. ^

Certified nurse midwives effects on catecholamine levels and maternal anxiety during labor

Studies of nurse midwifery care in the last twenty one years have reported excellent birth outcomes (Levy, Wilkenson and Marine, 1971; Platt et al. 1985; Stone et al. 1976). These outcomes are frequently attributed to the special support offered during labor and delivery by nurse midwives. This supportive style is thought to decrease catecholamine levels by reducing maternal anxiety. This prospective observational study evaluated catecholamine levels, anxiety levels, in-hospital costs, obstetrical practices and outcomes between low risk, term, labor and delivery primigravida patients managed by obstetrical residents (n = 55) or by certified nurse-midwives CNM (n = 59). The two groups were similar with regard to obstetrical risk factors present at admission. Each group was selected over the same period of time between March 23, 1994 and November 2, 1994. Specific catecholamines evaluated were epinephrine and norepinephrine. Obstetrical and newborn characteristics were also compared. This study did not prove that there is a decreased level in stress as indicated by lower levels of epinephrine and norepinephrine in nurse-midwife patients compared to obstetrical resident patients after adjusting for the use of epidural anesthesia. There was also no difference found in the perceived anxiety levels between the two groups. This study did confirm that nurse-midwives and obstetrical residents have different practice styles. Nurse-midwife patients had fewer augmented deliveries, fewer operative deliveries, less blood loss, fewer episiotomies and fewer third and fourth degree lacerations. The physician's choice to utilize more interventions such as continuous fetal monitoring and epidural anesthesia did not improve outcomes. The hospital cost of the nurse-midwife patients in this study was 35 percent lower than the physician patients. ^

Content of prenatal care and spontaneous preterm birth: Findings from the 1988 National Maternal and Infant Health Survey

The purposes of this study were to examine (1) the relationship between selected components of the content of prenatal care and spontaneous preterm birth; and (2) the degree of comparability between maternal and caregivers' responses regarding the number of prenatal care visits, selected components of the content of prenatal care, and gestational age, based on analyses of the 1988 National Maternal and Infant Health Survey conducted by the National Centers for Health Statistics. Spontaneous preterm birth was subcategorized into very preterm and moderately preterm births, with term birth as the controls. The study population was limited to non-Hispanic Anglo- and African-American mothers. The racial differences in terms of birth outcomes were also compared.^ This study concluded that: (1) there was not a high degree of comparability (less than 80%) between maternal and prenatal care provider's responses regarding the number of prenatal care visits and the content of prenatal care; (2) there was a low degree of comparability (less than 50%) between maternal and infant's hospital of delivery responses regarding gestational age at birth; (3) there were differences in selected components of the content of prenatal care between the cases and controls, overall and stratified by ethnicity (i.e., hemoglobin/hematocrit test, weight measurement, and breast-feeding counseling), but they were confounded with missing values and associated preterm delivery bias; (4) there were differences in selected components of the content of prenatal care between Anglo- and African-American cases (i.e., vitamin/mineral supplement advice, weight measurement, smoking cessation and drug abuse counseling), but they, too, were difficult to interpret definitively due to item nonresponse and preterm delivery biases; (5) no significant predictive association between selected components of the content of prenatal care and spontaneous preterm birth was found; and (6) inadequate/intermediate prenatal care and birth out of wedlock were found to be associated with moderately preterm birth.^ Future research is needed to examine the validity of maternal and prenatal care providers' responses and identify the sources of disagreement between their responses. In addition, further studies are needed to examine the relationship between the quality of prenatal care and preterm birth. Finally, the completeness and quality of patient and provider data on the utilization and content of prenatal care needs to be strengthened in subsequent studies. ^

An investigation of the pica practices of pregnant women in Houston and Prairie View, Texas

Pregnant African American women are at higher risk of having a preterm delivery and/or a low birthweight infant. Many factors are associated with adverse pregnancy outcomes but a food habit that deserves further study in the causal process is pica, a craving for, and ingestion of, nonnutritive substances such as laundry starch, clay, dirt, or ice. This food habit is more common in the African American population but has not been adequately studied in relation to preterm and/or low birth weight infants.^ Mothers (n = 281) with infants less than one year of age who participated in the Special Supplementary Food Program for Women, Infants, and Children (WIC) at clinics in Houston and Prairie View, Texas were interviewed regarding pica practices during pregnancy, dietary practices, and some demographic indices. Hospital records were abstracted for health information on the mothers and infants, including birthweight and gestational age at birth of the infant.^ The subjects were 88.6% African American, 6.8% Hispanic, and 4.6% Caucasian. Overall prevalence of pica was 76.5%. Pica prevalence by substance(s) was as follows: ice 53.7%; ice and freezer frost 14.6%; other substances such as baking soda, baking powder, cornstarch, laundry starch, and clay or dirt 8.2%; and 23.5% reported no pica. The women who reported ice/freezer frost pica had a higher percentage of illegal drug use and alcohol use during pregnancy. The women who reported other pica substances had the lowest mean educational level, highest gravidity, and a higher percentage smoked during pregnancy.^ There were no significant differences in nutrient intakes measured by the mean 24-hour dietary recalls between women who reported ice pica (n = 103) and women who denied pica (n = 50). The women who reported ice/freezer frost pica or other pica substances had more food cravings and food dislikes during pregnancy than those who reported ice pica or no pica.^ There were no differences in mean birthweight or mean gestational age at birth of infants born to mothers from the three pica groups and the no pica group but regression analyses revealed a possible relationship between pica, low maternal hemoglobin at delivery, and preterm birth. ^

The door of the tomb is open: Participatory action research to assess the impact of strengthened community capacity on maternal health care in rural Mali

This participatory action-research project addressed the hypothesis that strengthened community and women's capacity for self-development will lead to action to address maternal health problems and the prevention of maternal morbidity and mortality in Mali. Research objectives were: (1) to undertake a comparative cross-sectional study of the association of community capacity with improved maternal health in rural areas of Sanando, Mali, where capacity building interventions have taken place in some villages but not in others. (2) to describe women's maternal health status, access to and use of maternal health services given their residence in program or comparison communities.^ The participatory action research project was an integrated qualitative and quantitative study using participatory rural appraisal exercises, semi-structured group interviews and a cross-sectional survey.^ Factors related to community capacity for self-development were identified: community harmony; an understanding of the benefits of self-development; dynamic leadership; and a structure to implement collective activities.^ A distinct difference between the program and comparison villages was the commitment to train and support traditional birth attendants (TBAs). The TBAs in the program villages work in the context of the wider, integrated self-development program and, 10 years after their initial training, the TBAs continue to practice.^ Many women experience labor and childbirth alone or are attended by an untrained relative in both program and comparison villages. Nevertheless a significant change is apparent, with more women in program villages than in comparison villages being assisted by the TBAs. The delivery practices of the TBAs reveal the positive impact of their training in the "three cleans" (clean hands of the assistant, clean delivery surface and clean cord-cutting). The findings of this study indicate a significant level of unmet need for child spacing methods in all villages.^ The training and support of TBAs in the program villages yielded significant improvements in their delivery practices, and resulting outcomes for women and infants. However, potential exists for further community action. Capacities for self-development have not yet been directed toward an action plan encompassing other Safe Motherhood interventions, including access to family planning services and emergency obstetric care services. ^

Patterns of care and outcomes for pregnant inmates and their infants in Texas state prisons: Epidemiologic and ethnographic analyses

Female inmates make up the fastest growing segment in our criminal justice system today. The rapidly increasing trend for female prisoners calls for enhanced efforts to strategically plan the correctional facilities that address the needs of this growing population, and to work with communities to prevent crime in women. The incarcerated women in the U.S. have an estimated 145,000 minor children who are predisposed to unique psychosocial problems as a result of parental incarceration.^ This study examined the patterns of care and outcomes for pregnant inmates and their infants in Texas state prisons between 1994 and 1996. The study population consists of 202 pregnant inmates who delivered in a 2-year period, and a randomly sampled comparison cohort of 804 women from general Texas population, matched on race and educational levels. Both quantitative and qualitative data were used to elucidate the inmates' risk-factor profile, delivery/birth outcomes, and the patterns of care during pregnancy. The continuity-of-care issues for this population were also explored.^ Epidemiologic data were derived from multiple record systems to establish the comparison between two cohorts. A significantly great proportion of the inmates have prior lifestyle risk-factors (smoking, alcohol, and illicit drug abuse), poorer health status, and worse medical history. However, most of these existing risk-factors seem to show little manifestation in their current pregnancy. On the basis of maternal labor/delivery outcome and a number of neonatal indicators, this study found some evidence of a better pregnancy outcome for the inmate cohort when compared to the comparison group. Some possible explanations of this paradox were discussed. Seventeen percent of inmates gave birth to infants with suspected congenital syphilis. The placement patterns for the infants' care immediately after birth were elucidated.^ In addition to the quantitative data, an ethnographic approach was used to collect qualitative data from a subset of the inmate cohort (n = 20) and 12 care providers. The qualitative data were analyzed for their contents and themes, giving rise to a detailed description of the inmates' pregnancy experience. Eleven themes emerged from the study's thematic analysis, which provides the context for interpreting the epidemiologic data.^ Meaningful findings in this study were presented in a three-dimensional matrix to shed light on the apparent relationship between outcome indicators and their potential determinants. The suspected "linkages" between the outcome and their determinants can be used to generate hypotheses for future studies. ^

Prenatal care content and utilization among pregnant women enrolled in managed care programs in Harris County, Texas

This research study was conducted as a descriptive study of prenatal care experiences of women enrolled in public and private managed care programs. The study's aim was to describe the demographic characteristics of the women in the study and to analyze and compare their prenatal care experiences. ^ The objective of this study was to examine the research question: Do pregnant women enrolled in Medicaid Managed Care receive the same level of care as women enrolled in other Managed Care Programs in Harris County, Texas? ^ The study population was a convenience sample of pregnant women enrolled in managed care programs who presented to one of the two hospital study sites for delivery of their infant. The study utilized a self administered survey to measure adequacy and content of prenatal care received by the women during this pregnancy. Adequacy of prenatal care utilization was determined based on the Kessner Index criteria of timing of initiation of care and number of visits. Content of care was measured by the number of different medical services the women reported they had received and the number of health information topics the women reported on which they had received information. Demographic characteristics were described with univariate and bivariate statistics of frequencies and cross tabulations. Associations were evaluated using measures of linear correlations. ^ Results from the study showed there is an association between enrollment in Medicaid Managed Care (public) and prenatal care received compared to women enrolled in other Managed Care Programs (private). The results were derived from statistical tests on data the postpartum women gave when they completed the self-administered survey. Provider type was a moderate predictor of quality and quantity of prenatal care. The results also indicate that in the study population, minority ethnicity, income and lower educational status were associated with intermediate and inadequate prenatal care. ^

Examination of the engraftment of exogenous mesenchymal stem cells in ovarian tumors and their potential use as delivery vehicles for therapeutic genes

Interactions between neoplastic cells and the host stroma play a role in both tumor cell migration and proliferation. Stromal cells provide structural support for malignant cells, modulate the tumor microenvironment, and influence phenotypic behavior as well as the aggressiveness of the malignancy. In response, the tumor provides growth factors, cytokines, and cellular signals that continually initiate new stromal reactions and recruit new cells into the microenvironment to further support tumor growth. Since growing tumors recruit local cells, as well as supplemental cells from the circulation, such as fibroblasts and endothelial precursors, the question arises if it would be possible to access circulating stromal cells to modify the tumor microenvironment for therapeutic benefits. One such cell type, mesenchymal stem cells (MSC), could theoretically be engrafted into stroma. MSC are pluripotent cells that have been shown to form stromal elements such as myofibroblasts, perivascular tissues and connective tissues. Several reports have demonstrated that MSC can incorporate into sites of wound healing and tissue repair, due to active tissue remodeling and local paracrine factors, and given the similarity between wound healing and the carcinoma induced stromal response one can hypothesize that MSC have the potential to be recruited to sites of tumor development. In addition, gene-modified MSC could be used as cellular vehicles to deliver gene products into tumors. My results indicate that MSC home to and participate in tumor stroma formation in ovarian tumor xenografts in mice. Additionally, once homed to tumor beds, MSC proliferate rapidly and integrate. My studies aim at understanding the fate of MSC in the tumor microenvironment, as well as utilizing them for cellular delivery of therapeutic genes into the stroma of ovarian carcinomas. ^