The effects of adequacy and content of prenatal care on birth outcomes in a high -risk Missouri population

The purpose of this observational study was investigation of the relationship between quantitative adequacy of prenatal care, specific prenatal care content and pregnancy outcome in a high risk Missouri population. A sample of 1484 women from three Missouri regions known to have high rates of low birth weight, infant mortality, and inadequate prenatal care rates participated in structured post-partum interviews. Approximately one-half of the sample had received adequate prenatal care and the other half inadequate prenatal care as determined by an index utilized by the Missouri Department of Health.^ Prenatal care content was assessed by reports of prenatal education in six different areas: Diet, smoking, alcohol, drug, preterm labor counseling, and advice on when to call the health provider if preterm labor was suspected by the woman. Low birth weight, in both term and preterm infants, were the two birth outcomes examined. A variety of maternal socio-demographic variables were also considered.^ The results of this study suggest that specific educational content, delivered during prenatal care, may have lessen the risk of giving birth to a preterm-low birth weight infant. Prenatal education for recognition of preterm labor, and advice on when to call the health provider if preterm labor was suspected were found to be associated with a decreased risk of preterm delivery. Specific educational content was not, however, associated with risk of term-low weight birth nor was quantitative adequacy of care associated with the risk of either term- or preterm-low birth weight.^ These findings reinforce a body of literature which stresses the importance of appropriate prenatal care in preventing preterm low birth weight. Additionally, the findings suggest interventions that may be specifically effective for prematurity prevention. ^

Behavioral decision making and the levels of change: An application of the transtheoretical model to prenatal smoking in low -income women

Despite continued research and public health efforts to reduce smoking during pregnancy, prenatal cessation rates in the United States have decreased and the incidence of low birth weight has increased from 1985 to 1991. Lower socioeconomic status women who are at increased risk for poor pregnancy outcomes may be resistant to current intervention efforts during pregnancy. The purpose of this dissertation was to investigate the determinants of continued smoking and quitting among low-income pregnant women.^ Using data from cross-sectional surveys of 323 low-income pregnant smokers, the first study developed and tested measures of the pros and cons of smoking during pregnancy. The original decisional balance measure for smoking was compared with a new measure that added items thought to be more salient to the target population. Confirmatory factor analysis using structural equation modeling showed neither the original nor new measure fit the data adequately. Using behavioral science theory, content from interviews with the population, and statistical evidence, two 7-item scales representing the pros and cons were developed from a portion (n = 215) of the sample and successfully cross-validated on the remainder of the sample (n = 108). Logistic regression found only pros were significantly associated with continued smoking. In a discriminant function analysis, stage of change was significantly associated with pros and cons of smoking.^ The second study examined the structural relationships between psychosocial constructs representing some of the levels of and the pros and cons of smoking. The cross-sectional design mandates that statements made regarding prediction do not prove causation or directionality from the data or methods analysis. Structural equation modeling found the following: more stressors and family criticism were significantly more predictive of negative affect than social support; a bi-directional relationship was found between negative affect and current nicotine addiction; and negative affect, addiction, stressors, and family criticism were significant predictors of pros of smoking.^ The findings imply reversing the trend of decreasing smoking cessation during pregnancy may require supplementing current interventions for this population of pregnant smokers with programs addressing nicotine addiction, negative affect, and other psychosocial factors such as family functioning and stressors. ^

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. ^

An examination of the relationship between maternal and neighborhood-level characteristics and intrauterine growth retardation in Harris County, Texas, 1999--2001

The persistence of low birth weight and intrauterine growth retardation (IUGR) in the United States has puzzled researchers for decades. Much of the work that has been conducted on adverse birth outcomes has focused on low birth weight in general and not on IUGR. Studies that have examined IUGR specifically thus far have focused primarily on individual-level maternal risk factors. These risk factors have only been able to explain a small portion of the variance in IUGR. Therefore, recent work has begun to focus on community-level risk factors in addition to the individual-level maternal characteristics. This study uses Social Ecology to examine the relationship of individual and community-level risk factors and IUGR. Logistic regression was used to establish an individual-level model based on 155, 856 births recorded in Harris County, TX during 1999-2001. IUGR was characterized using a fetal growth ratio method with race/ethnic and sex specific mean birth weights calculated from national vital records. The spatial distributions of 114,460 birth records spatially located within the City of Houston were examined using choropleth, probability and density maps. Census tracts with higher than expected rates of IUGR and high levels of neighborhood disadvantage were highlighted. Neighborhood disadvantage was constructed using socioeconomic variables from the 2000 U.S. Census. Factor analysis was used to create a unified single measure. Lastly, a random coefficients model was used to examine the relationship between varying levels of community disadvantage, given the set of individual-level risk factors for 152,997 birth records spatially located within Harris County, TX. Neighborhood disadvantage was measured using three different indices adapted from previous work. The findings show that pregnancy-induced hypertension, previous preterm infant, tobacco use and insufficient weight gain have the highest association with IUGR. Neighborhood disadvantage only slightly further increases the risk of IUGR (OR 1.12 to 1.23). Although community level disadvantage only helped to explain a small proportion of the variance of IUGR, it did have a significant impact. This finding suggests that community level risk factors should be included in future work with IUGR and that more work needs to be conducted. ^

Prenatal care programs in a clinic based center in El Paso, Texas: Evaluating outcomes among Hispanic women

Early prenatal care has been found to improve pregnancy and birth outcomes by reducing the risk of low birth weight and preterm births. Statistics point to lower utilization rates of prenatal care in El Paso, Texas and increasing rates of low birth weight. This study was a secondary data analysis, which explored the perceived benefits and barriers known to influence the utilization of prenatal care, and the birth outcomes among participating subjects attending three different prenatal care programs offered at the Centro San Vincent Clinic during the period of December 2006 to February 2008. A survey was used to collect data on demographics and assess perceived benefits and barriers regarding early prenatal care and self-efficacy of the participants. Post-partum birth records were used to gather data about the participant's newborns to include birth weight, gestational age, and the type of delivery (i.e. vaginal versus Cesarean birth). Chi square analysis was conducted to test for significant differences and associations. The sample of women in the study had high risk factors for inadequate utilization of prenatal care. In spite of high demographic risk factors, these women had higher perceived benefits, lower perceived barriers and high self-efficacy associated with prenatal care utilization. The perceived benefits and barriers to prenatal care were associated with place of birth and language preferred, with women from Mexico and who preferred Spanish having higher perceived benefits and lower barriers. There was no significant difference in birth outcomes among the women in different prenatal care programs. The findings of this study suggest that of all participants in the study, those born in Mexico demonstrated higher rates of perceived benefits of early prenatal care. The analysis also suggested that healthy birth outcomes were evenly distributed among women participating in one of the three prenatal care programs. ^

Probiotics and the prevention of necrotizing enterocolitis in preterm infants: A systematic review of the literature

Necrotizing enterocolitis is a common gastrointestinal disease associated with high mortality and morbidity among preterm infants. This was a systematic literature review that evaluated whether the administration of probiotic supplements is of benefit in the prevention of NEC. The search was narrowed to randomized clinical trials identified through The Cochrane Central Register of Controlled Trials, U.S. National Institute of Health clinical trials registry database, Pub Med and OVID MEDLINE databases. Inclusion criteria were: prospective, randomized clinical trials that administered probiotics as a preventive measure against NEC for infants of early gestational age (<35 wks) and/or low birth weight (<1500g), maintained NEC as the primary measured outcome, used Bell’s classification for NEC diagnosis with reports of stage 2 NEC or higher, and began probiotic administration within 10 days of life. Trials were excluded if participant enrollment was fewer than 100 infants, published before the year 2000, or probiotic supplementation was discontinued after less than seven consecutive days. Based on specific study characteristics, each resulting article was then judged by two authors for study quality. The search was further narrowed to studies of either high or moderate quality, which were then summarized in a set of tables based on study characteristics and results. From an initial set of 20 identified studies, five clinical trials met all criteria; each was discussed thoroughly based on trial limitations, strengths and comparisons to other included publications. Based on this review, the weight of evidence appears to support the use of probiotic supplementation in preterm infants as a preventive measure against NEC. Recommendations for future research were also provided.^

Factors affecting prenatal care use and pregnancy outcome in Texas: A comparative study among and within Black, Anglo, and Hispanic populations

This research project is a study in the field of public health to test the relationships of demographic, socioeconomic, behavioral, and biological factors with (1) prenatal care use and (2) pregnancy outcome, measured by birth weight. It has been postulated that demographic, socioeconomic, and behavioral factors are associated with differences in the use of prenatal care services. It has also been postulated that differences in demographic, socioeconomic, behavioral, and biological factors result in differences in birth weight. This research attempts to test these two basic conceptual frameworks. At the same time, an attempt is made to determine the population groups and subgroups that are at increased risk (1) of using fewer prenatal care visits, and (2) of displaying a higher incidence of low birth weight babies. An understanding of these relationships of the demographic, socioeconomic, behavioral, and biological factors in the use of prenatal care visits and pregnancy outcome, measured by birth weight, will potentially offer guidance in the planning and policy development of maternal and child health services. The research considers four major components of maternal characteristics: (1) Demographic factors. Ethnicity, household size, maternal parity, and maternal age; (2) Socioeconomic factors. Maternal education, family income, maternal employment, health insurance coverage, and household dwelling; (3) Behavioral factors. Maternal smoking, attendance at child development classes, mother's first prenatal care visit, total number of prenatal care visits, and adequacy of care; and, (4) Biological factors. Maternal weight gain during pregnancy.^ The research considers 16 independent variables and two dependent variables.^ It was concluded that: (1) Generally, differences in demographic, socioeconomic, and behavioral factors were associated with differences in the average number of prenatal care visits between and within population groups and subgroups. The Hispanic mothers were the lowest users of prenatal care services. (2) In some cases, differences in demographic, socioeconomic, behavioral, and biological factors demonstrated differences in the average birth weight of infants between and within population groups and subgroups. (3) Differences in demographic, socioeconomic, behavioral, and biological factors resulted in differences in the rates of low birth weight babies between and within population groups and subgroups. The Black mothers delivered the highest incidence of low birth weight infants.^ These findings could provide guidance in the formulation of public health policies such as MCH services, an increase in the use of prenatal care services by prospective mothers, resulting in reduction of the incidence of low birth weight babies, and consequently aid in reducing the rates of infant mortality. ^

The social construction of infant mortality: From grassroots to medicalization

Infant mortality as a problematic situation has been recognized for some 130 years in one form or another. It has undergone various changes in its empirical dimensions relative to whom we study within the population, what we study--low birth-weight vs. pre-term births--and how we study it--whether demographically or medically. An analysis of the process by which the condition was raised by claims makers as an intolerable situation among America's urban residents reveals that demographic and medical data were sparse. Nonetheless, a judgement about the meaning and significance of the condition was made, and that interpretation led to the promulgation of systems to both document and address the condition as it has come to be defined.^ This investigation depicts the historical context and natural history of infant mortality as one of a number of social problems that came to be defined through the interplay among groups and individuals making claims and how their claims came to the public policy agenda as worthy of collective resources--who won, who lost and why. The process of social definition focuses attention on the claims makers and the ways they contrast the meaning, origins and remedies for this troubling condition. The historical context becomes the frame of reference for understanding the actions of the claims makers and the meaning and significance they attached to the problem.^ We purport that "context" provides a closer reality than disjoined "value free" accounts. Context provides the evidence for the definition, who participated in the process, why and by what means.^ The role of women in the definitional process reveals the differences in approaches utilized by the women of the settlement house reform movement and African-American women working at the grass-roots. Much of the work done by these two groups provided options to the problem's remedy; however, their differences paved the way to our current (principally medically-oriented) definition and its inherent limitations. ^

Sudden Infant Death disparities: A systematic review on health education and policy recommendations for decreasing Sudden Infant Death in the African-American community

Objective: To perform a systematic review of the literature on SIDS and SUID deaths concentrated in the African-American community, describe health education and policy recommendations and recommend a new approach that may aid in decreasing the disparity of infant mortality in the African-American community. ^ Methods: The PubMed database was systematically searched to identify relevant articles for final review and analysis. Using the CASP 2006 system to critique literature, twelve articles were found that met inclusion and exclusion criteria. ^ Results: Evidence in the literature confirmed there was a current disparity among African Americans' infant mortality rates in comparison to other US ethnic groups. The underlying reasons for these disparities included the following maternal and infant characteristics: mothers younger than eighteen, having more than one live infant, having a high school education or less, never been married, and have infants born preterm or with low birth weight. Maternal smoking, substance abuse, and breastfeeding did not have a significant impact on infant sleep environments among African Americans. ^ Conclusion: Tailored health education programs at the community level, better access to pre-pregnancy and prenatal care, and increased maternal perception of risk that is relevant to the infants sleeping environment are all possible solutions that may decrease African American infant mortality rates.^

Black/white disparities in infant mortality rates in the U.S.: A quality of care perspective

The infant mortality rate for non-Hispanic Black infants in the U.S. is 13.63 deaths per 1,000 live births while the IMR for non-Hispanic White persons in the U.S. is 5.76 deaths per 1,000 live births. Black women are 2 times as likely as White women to deliver preterm infants and Black women are 2 times as likely as White women to deliver low birth weight infants (weighing less than 2,500 grams at birth). Differential underlying risk factors among mothers of different racial/ethnic groups for delivering pre-term and low birth weight infants have been historically accepted as the cause of racial disparities in IMRs. However, differential underlying risk status may not be the only major causative factor. Differential or unequal access to and provision of care is widely speculated to be a leading contributing factor to the wide racial disparity in infant mortality.2 This paper conducts a systematic review of existing literature investigating racial disparities in obstetrical care provided by healthcare practitioners to evaluate whether inequities in healthcare services provided to pregnant mothers and their neonates exist. The search terms "racial disparities obstetrical care," "racial differences quality of prenatal care," and "infant mortality racial disparities" were entered into the EBSCO Medline, Ovid Medline, PubMed, and Academic Search Complete databases, and articles between years 1990–2011 were selected for abstract review. The only articles included were those that used statistical methods to assess whether racial inequalities were present in the obstetrical services provided to pregnant women. My literature search returned 5 articles. Four of the five studies yielded significant racial differences in obstetrical care. However, the one study that used a large, nationally representative valid sample did not represent significant differences. Thus, this review provides initial evidence for racial disparities in obstetrical care, but concludes that more studies are needed in this area. Not all of the studies reviewed were consistent in the use and measurement of services, and not all studies were significant. The policy and public health implications of possible racial disparities in obstetrical care include the need to develop standard of care protocols for ALL obstetrical patients across the United States to minimize and/or eliminate the inequities and differences in obstetrical services provided.^

EFFECT OF ANCHORING ON PERCEIVED AMNIOCENTESIS RELATED MISCARRIAGE RISK WITHIN A LATINA POPULATION

Most recognized pregnancies are completed without difficulty, yet there is always a 3-5% background risk to have a child with a birth defect. Amniocentesis, the most common type of prenatal diagnostic test, is used to detect chromosomal abnormalities, such as Down syndrome. Amniocentesis is associated with a risk of complications that can lead to a miscarriage, which is typically quoted to be between 1 in 300 and 1 in 500. Amniocentesis uptake rates are typically lowest within the Latina community, and although the factors related to this have been studied before, no specific conclusions have been reached. The general population has a difficult time interpreting risks, as individuals vary in numeracy skills as well as personal factors that can influence risk perception. A recent study by Nuccio (2010) investigated the effect of anchoring, where a patient’s prior knowledge about a subject affects her risk perception, and how it relates to the uptake of amniocentesis within a diverse population in Houston, TX. The effect of anchoring on perceived amniocentesis-related miscarriage risk within the Latina population has not been previously examined. A two-part questionnaire was completed by 96 Latinas receiving prenatal genetic counseling due to an increased risk to have a baby with a chromosome abnormality at various clinics in Houston, TX. The genetic counselor involved in the session completed a separate survey. This population was largely unfamiliar with surveys, risk figures, and prenatal testing. Only one individual was able to quantify the risk associated with amniocentesis prior to the genetic counseling. While the majority of women felt that the risk association with amniocentesis is very low to average, only 7 individuals pursued diagnostic testing through amniocentesis. Most women did not feel like the information gained from an amniocentesis would change the management of their pregnancy and/or they did not believe that their baby had a problem. Women, regardless of ethnicity, deserve individualized genetic counseling sessions that cater to their needs and desires regarding their prenatal care.

Molecular characterization of a gene required for entry into S phase of the mitotic cell cycle in the yeast {\it Saccharomyces cerevisiae\/}

A strain of Saccaromyces cerevisiae (SC3B) with a temperature sensitive defect in the synthesis of DNA has been isolated. This defect is due to a single recessive mutation in a gene named INS1 required for the initiation of S phase. Arrested cells carrying the ins1$\sp{ts}$ allele are defective in the completion of G1 to S phase transition events including SPB duplication or separation, initiation of DNA synthesis, normal control of budding, and bud neck stability. The mutation and a gene which complements the mutation were mapped to chromosome IV. The complementing gene was proved to be the wild type allele of the temperature sensitive mutation by genetic linkage of an integrated clone. A very low abundance 4.2 kb RNA message was observed in the strain SC3B which increased greatly in this strain transformed with a multiple copy plasmid carrying the complementing clone. The wild type gene was sequenced and found to encode a 1268 amino acid protein of with a molecular weight of 142,655 Daltons. Computer assisted searches for similar DNA sequences revealed no significant homology matches. However, searches for protein sequence homology revealed a protein (the DIS3 gene product of S. pombe) with a similar sequence over a 534 amino acid stretch to the predicted INS1 gene product. A later search revealed a near identical sequence for a gene (SRK1) also isolated from S. cerevisiae. ^

Differences in small-for-gestational-age and preterm birth among Asian subgroups in relation to nativity status

This retrospective cohort study examined the association between nativity status and very preterm birth, preterm birth, and small-for-gestational-age (SGA) among Asian subgroups using Texas birth certificate data with no personal identifiers. A total of 877,322 birth certificates of Asian and US-born white women with a singleton birth in Texas from 2001-2004 were analyzed. Birth certificate records of US-born white, Chinese, Japanese, Korean, Vietnamese, Filipino, and Asian Indian women with a singleton birth were included in the analysis. Logistic regressions models were used to explore and understand the differences of the effect of nativity status on birth outcomes in Asian subgroups with US-born whites as the reference group. Most of the Asian subgroups had a lower risk of preterm births compared with US born whites, with reductions in risk ranging from 19% to 49% and the lowest risk of preterm birth observed among foreign-born Chinese mothers. Only Filipino mothers had a higher risk of preterm birth compared to US-born whites. Overall, foreign-born Asians had lower risks for very preterm birth and preterm birth than US-born Asians and US-born whites. US-born Asians were at higher risk for preterm birth than US-born whites. For SGA, all Asian subgroups and Asian subgroups by nativity status were at higher risk of SGA than US-born whites. Asian Indians and Japanese were at highest risk for SGA infants with 2.5 to 3 times the risk of SGA present in US-born whites. Foreign-born Asian women were at higher risk for SGA than their US-born counterparts. This study showed that health disparities among Asian subgroups are hidden by classifying Asians into a single group. By examining Asian subgroups separately and looking at nativity status, the differences in risk of SGA and preterm birth can be revealed so prevention efforts can focus on high risk groups. ^

Epidemiology of isolated obstructive genitourinary defect in Texas: 1999--2003

Background. Obstructive genitourinary defects include all anomalies causing obstruction anywhere along the urinary tract. Previous studies have noted a large excess of males among infants affected by these types of defects. This is the first epidemiologic study focused solely on obstructive genitourinary defects (OGD). ^ Methods. Data on 1,683 mild and 302 severe cases of isolated OGD born between 1999 and 2003 and ascertained by the Texas Birth Defects Registry were compared to all births in Texas during the same time period. Adjusted prevalence odds ratios (POR) were calculated for infant sex, birth weight, gestational age, mother’s race/ethnicity, mother’s age, mother’s education, parity, birth year, start of prenatal care, multiple birth, and public health region of birth. Severe cases were defined as those cases that died prior to birth, died after birth, or underwent surgery for OGD in the first year of life. Cases of OGD that had other major birth defects besides OGD were excluded from this study. ^ Results. Severe cases of OGD were more likely than mild cases to have multiple obstructive genitourinary anomalies (37.8% vs. 18.9%) and bilateral defects (40.9% vs. 31.3%). Males had a significantly greater risk of OGD than females for both severe and mild cases: adjusted POR = 3.26 (95% CI = 2.45-4.33) and adjusted POR = 2.60 (95% CI = 2.33-2.90), respectively. Infants with both severe and mild OGD were more likely to be very preterm birth at birth compared with infants without OGD: crude POR of 16.19 (95% CI = 10.60-24.74) and 4.75 (95% CI = 3.54-6.37), respectively. Among the severe group, minority races had a decreased risk of OGD with an adjusted POR of 0.74 (95% CI = 0.55-0.98) compared with whites. Among the mild cases, increased rates of OGD were found in older mothers (adjusted POR = 1.10, 95% CI = 1.05-1.15), college/higher educated mothers (adjusted POR = 1.07, 95% CI = 1.01-1.13) and multiple births (adjusted POR = 1.28, 95% CI = 1.01-1.62). There was also a decreased risk of mild cases among black mothers compared to whites (adjusted POR = 0.63, 95% CI = 0.52-0.76). Compared to 1999, the prevalence of mild cases of OGD increased significantly over the 5 year study period with an adjusted POR of 1.10 (95% CI = 1.06-1.15) by 2003. ^ Conclusion. Risk factors of OGD for both severe and mild forms were male sex and preterm birth. Severe cases were more likely to have multiple OGD defects and be affected bilaterally. An increase in prevalence of mild cases of OGD over time and differences in rates of black, older, and higher educated mothers in mild cases may be attributed to ultrasound use. ^

INTERACTION BETWEEN BRK AND HER2 IN BREAST CANCER

INTERACTION BETWEEN BRK AND HER2 IN BREAST CANCER Midan Ai, Ph.D. Supervisory Professor: Zhen Fan, M.D. Breast tumor kinase (Brk) is a nonreceptor protein-tyrosine kinase that is highly expressed in approximately two thirds of breast cancers but is not detectable or is expressed at very low levels in normal mammary epithelium. Brk plays important roles in promoting proliferation, survival, invasion, and metastasis of breast cancer cells, but the mechanism(s) of which remain largely unknown. Recent studies showed that Brk is frequently co-overexpressed with human epidermal growth factor receptor-2 (HER2) and is physically associated with HER2 in breast cancer. The mechanism needs to be determined. In my studies, I found that high expression of HER2 is correlated with high expression of Brk in breast cancer cell lines. Silencing HER2 expression via RNA interference in HER2 over-expressed breast cancer cells resulted in Brk protein decrease and overexpression of HER2 in HER2 low-expressed breast cancer cells up-regulated Brk expression. The mechanism study indicated that overexpression of HER2 increased Brk protein stability. Brk was degraded through a Ca2+-dependent protease pathway involving calpain and HER2 stimulated Brk expression via inhibiting calpain activity. Calpastatin is a calpain endogenous inhibitor and the calpain-calpastatin system has been implicated in a number of cell physiological functions. HER2 restrained calpain activation via up-regulating calpastatin expression and HER2 downstream signaling, MAPK pathway, was involved in the regulation. Furthermore, silencing of Brk expression by RNA interference in HER2-overexpressing breast cancer cells decreased HER2-mediated cell proliferation, survival, invasion/metastasis potential and increased cell sensitivity to HER2 kinase inhibitor, lapatinib, treatment, indicating that Brk plays important roles in regulating and mediating the oncogenic functions of HER2. The Stat3 pathway played important roles in Brk mediated cell survival and invasion/metastasis in the context of HER2-overexpressing breast cancer cells. However, transgenic mice with inducible expression of constitutively active Brk (CA) in the mammary epithelium failed to develop malignant change in the mammary glands after Brk induction for 15 months which indicated that expression of Brk protein alone was not sufficiently to induce spontaneous breast tumor. Bitransgenic mice with co-expression of HER2/neu and inducible expression of Brk in the mammary epithelium developed multifocal mammary tumors, but there were no significant difference in the tumor occurring time, tumor size, tumor weight and tumor multiplicity between the mouse group with co-expression of Brk and HER2/neu and the mouse group with HER2/neu expression only.