Alteration of AKT Activity Increases Chemotherapeutic Drug and Hormonal Resistance in Breast Cancer yet Confers an Achilles Heel by Sensitization to Targeted Therapy

The PI3K/PTEN/Akt/mTOR pathway plays critical roles in the regulation of cell growth. The effects of this pathway on drug resistance and cellular senescence of breast cancer cells has been a focus of our laboratory. Introduction of activated Akt or mutant PTEN constructs which lack lipid phosphatase [PTEN(G129E)] or lipid and protein phosphatase [PTEN(C124S)] activity increased the resistance of the cells to the chemotherapeutic drug doxorubicin, and the hormonal drug tamoxifen. Activated Akt and PTEN genes also inhibited the induction of senescence after doxorubicin treatment; a phenomenon associated with unrestrained proliferation and tumorigenesis. Interference with the lipid phosphatase domain of PTEN was sufficient to activate Akt/mTOR/p70S6K as MCF-7 cells transfected with the mutant PTEN gene lacking the lipid phosphatase activity [PTEN(G129E)] displayed elevated levels of activated Akt and p70S6K compared to empty vector transfected cells. Cells transfected with mutant PTEN or Akt constructs were hypersensitive to mTOR inhibitors when compared with the parental or empty vector transfected cells. Akt-transfected cells were cultured for over two months in tamoxifen from which tamoxifen and doxorubicin resistant cells were isolated that were >10-fold more resistant to tamoxifen and doxorubicin than the original Akt-transfected cells. These cells had a decreased induction of both activated p53 and total p21Cip1 upon doxorubicin treatment. Furthermore, these cells had an increased inactivation of GSK-3β and decreased expression of the estrogen receptor-α. In these drug resistant cells, there was an increased activation of ERK which is associated with proliferation. These drug resistant cells were hypersensitive to mTOR inhibitors and also sensitive to MEK inhibitors, indicating that the enhanced p70S6K and ERK expression was relevant to their drug and hormonal resistance. Given that Akt is overexpressed in greater than 50% of breast cancers, our results point to potential therapeutic targets, mTOR and MEK. These studies indicate that activation of the Akt kinase or disruption of the normal activity of the PTEN phosphatase can have dramatic effects on activity of p70S6K and other downstream substrates and thereby altering the therapeutic sensitivity of breast cancer cells. The effects of doxorubicin and tamoxifen on induction of the Raf/MEK/ERK and PI3K/Akt survival pathways were examined in unmodified MCF-7 breast cells. Doxorubicin was a potent inducer of activated ERK and to a lesser extent Akt. Tamoxifen also induced ERK. Thus a consequence of doxorubicin and tamoxifen therapy of breast cancer is the induction of a pro-survival pathway which may contribute to the development of drug resistance. Unmodified MCF-7 cells were also sensitive to MEK and mTOR inhibitors which synergized with both tamoxifen and doxorubicin to induce death. In summary, our results point to the key interactions between the PI3K/PTEN/Akt/mTOR and Raf/ MEK/ERK pathways in regulating chemotherapeutic drug resistance/sensitivity in breast cancer and indicate that targeting these pathways may prevent drug and hormonal resistance. Orignally published Advances in Enzyme Regulation, Vol. 48, No. 1, 2008

Hot Water Drench Treatments for the Control of Burrowing Nematode, Radopholus Similis, in Tropical Ornamentals

x, 71 leavesHot water drench treatments were investigated for their potential application as quarantine treatments against Radopholus similis, in two palms, Rhapis excelsa and Caryota mitis, and in potted Anthurium. Drenches with 50°C water were applied for 10 to 16 minutes to both R. excelsa and C. mitis. R. similis were eliminated from C. mitis in all treatments longer than 10 minutes. In R excelsa, a 16-minute hot water drench achieved 99.6% mortality of R. similis. In Anthurium, previous applications of hot water drench treatments resulted in a few survivors being detected 2 months after treatment. An experiment was designed to test cultivar effects, duration of time between treatment and nematode assay, and location of surviving nematodes after hot water drench treatment on four cultivars Anthurium. No cultivar differences were found in the reproductive factor of R. similis. Surviving nematodes, 1 week after treatment, were only found in stem sections above the soil line. Four weeks after treatment nematodes were found in roots and stems below the soil line, Migration into stem tissue is a proposed mechanism for escaping lethal temperatures. Conditioning treatments applied to Anthurium may also enhance thermotolerance in R. similis and decrease the efficacy of subsequent eradication treatments. R. simils did not survive challenge heat treatment after receiving a variety conditioning treatments in vitro. Probit regression estimates of conditioned and unconditioned R. similis mortality rates in potted Anthurium was similar. However survivors in conditioned potted Anthurium suggest that efficacy of eradication is compromised, although development of thermotolerance has not been confirmed

When OFW parents are not around: Health conditions of adolescents left behind and associated factors

Using a descriptive-quantitative research design, this study aimed to examine the health conditions of adolescents left behind (ages 13-17) by OFW-parents, and to define how their health is the outcome of their personal and lifestyle characteristics and their use of protective mechanisms. A total of 400 adolescents left behind by OFW-parents were selected via multi-stage area sampling and were surveyed by using a guided group self-administered questionnaire. Descriptive statistics and multivariate ordinal logistic regression were performed to analyze the data. Findings show that adolescents left behind by OFW parents rated themselves to have a fair or moderately healthy lifestyle and perceived themselves to have a strong protective mechanisms to manage their situation as a child of an OFW. Results also show that they perceived themselves to have a healthy or good overall health condition. On the health domains, they rated their physical and psychological health conditions as very healthy, their emotional condition as good or healthy, and their social and spiritual health conditions as moderately healthy. This study also found significant association of their overall health condition with their personal characteristics, lifestyle pattern, and with their use of protective mechanisms. Univariate analyses of their overall health condition show that 6 out of the 20 independent variables were significant, and that sex is the strongest predictor of their overall health condition with the female respondents having more likely to see their health condition as good or healthy most of the time compared to male respondents. On the health domains, good personal hygiene practices predicts their physical health condition, that is those with good personal hygiene practices are more likely to be physically healthy. The sex of the main care provider predicts their psychological health condition, that is those with female care provider are less psychologically healthy compared to those with male care provider. Their emotional health is predicted the most by their personal interests, that is those who engage in unhealthy lifestyle are less likely to be emotionally healthy. Their social health is predicted the strongest by their pattern of communication with the parent-away, that is those who do not have an open and regular pattern of communication with the parent away are less likely to be socially healthy compared to those who have an open and regular communication with the parent away. Lastly, their spiritual health condition is predicted the strongest by the absence of the mother, that is those with mother working as OFW tends to lacking on their spiritual health compared to those who have the mother staying and only the father works as OFW. Findings hope to help develop appropriate program/s of action that will strengthen the OFW family system

Social capital of left-behind children: Determinants and association with school performance

This study examined the influence of social capital on the school performance of left-behind children who were deprived of the physical presence of migrant parents. Social capital in the family, in school, and the community were examined through quantitative design. A survey was conducted among 384 left-behind children selected through multi-stage probability sampling. Results of regression analysis showed that higher levels of shared values and emotions in the family, social trust in the school, involvement in community life, and age of migrant parents determine a higher level of values learned. Higher levels of supportive relationship, social trust at school, and involvement in community life predict a higher level of right conduct. Higher levels of supportive relationship and supportive norms determine a higher average grade. Left-behind children with mother-present, father migrant draw more social capital in the family; while left-behind children with father-present, mother-migrant generate social capital in the school and the community. It is recommended that fathers should be involved in providing care and in the nurturing of left-behind children. Schools should cultivate an environment that invests in social capital especially for the left-behind children lacking in social capital at home. Government institutions serving for the welfare of migrant parents should educate and assist in the psycho-social needs of left-behind children and migrants’ households. © 2018 by De La Salle University

Filipino Adolescents’ Experiences of Abusive Parent-Child Relationship in Low Socioeconomic Status Families

This phenomenological-qualitative study aimed to describe how an abusive parent-child relationship of selected Filipino adolescents from an intact family of low socioeconomic status affects the perceptions of their potential romantic partner, marriage, and family. The study also uncovered their coping mechanisms and support system.  The seven informants were identified using a purposive sampling technique. The researchers devised an open-ended interview guide to elicit information from the informants and were conducted with a guidance counsellor. With the use of content analysis, the study revealed that their abusive experiences with one or both parents have significantly affected their perceptions. Most of them have resorted to using negative coping strategies and that their grandparents stood as their extended family support system with their friends as their non-family support system. The informants displayed a significantly entrenched position on the characteristics of their future marital partner and family. However, they have shown disapproval of marriage due to their experiences. The study also exposed that mothers have been more present in the abusive parent-child experiences than the fathers, which contradicts expectations that fathers act as strict disciplinarians and mothers being the child's protector in Philippine Culture. The study exposed the experiences of children in verbal and physical abuse in their homes from intact families with low socioeconomic status in Metro Manila, wherein expounds on the type of social support these children have been given and the kinds of coping mechanisms that are prevalent in their experiences and how these abusive parent-child experiences reflected with either positive or negative on their perception of marital partner, the concept of marriage, and concept of family, wherein provides substantial knowledge on how these experiences can be handled and faced in terms of treatment

Employees Work Engagement: Correlations with Employee Personal Characteristics, Organizational Commitment and Workplace Happiness

Using data collected from 76 employees of a manufacturing company in Manila, Philippines, this study conducted a correlation analysis to determine the relationship between the level of their engagement at work and their personal characteristics, organizational commitment in the workplace, and job satisfaction. A self-administered structured survey questionnaire was use in the survey. The collected data was analyzed using descriptive statistics to determine the mean scores, frequencies, and percentages, and parametric inferential statistics were employed to examine the correlations between variables. The results indicate a high level of employee work engagement and job satisfaction, as well as a moderate level of employee organizational commitment. Employee age, position and monthly salary were significantly correlated with employee work engagement. The level of employee engagement increases with age, position and income. Results also revealed a significant and strong positive correlation between the level of employee engagement and employee happiness at work. Implications for practices are offered