Engines of change: Nonmuscle myosin II in mechanobiology.

The emergence of mechanobiology has unveiled complex mechanisms by which cells adjust intracellular force production to their needs. Most communicable intracellular forces are generated by myosin II, an actin-associated molecular motor that transforms adenosine triphosphate (ATP) hydrolysis into contraction in nonmuscle and muscle cells. Myosin II-dependent force generation is tightly regulated, and deregulation is associated with specific pathologies. Here, we focus on the role of myosin II (nonmuscle myosin II, NMII) in force generation and mechanobiology. We outline the regulation and molecular mechanism of force generation by NMII, focusing on the actual outcome of contraction, that is, force application to trigger mechanosensitive events or the building of dissipative structures. We describe how myosin II-generated forces drive two major types of events: modification of the cellular morphology and/or triggering of genetic programs, which enhance the ability of cells to adapt to, or modify, their microenvironment. Finally, we address whether targeting myosin II to impair or potentiate its activity at the motor level is a viable therapeutic strategy, as illustrated by recent examples aimed at modulating cardiac myosin II function in heart disease.

Panobinostat Synergistically Enhances the Cytotoxicity of Microtubule Destabilizing Drugs in Ovarian Cancer Cells.

Ovarian cancer (OC) is one of the most common gynecologic neoplasia and has the highest mortality rate, which is mainly due to late-stage diagnosis and chemotherapy resistance. There is an urgent need to explore new and better therapeutic strategies. We have previously described a family of Microtubule Destabilizing Sulfonamides (MDS) that does not trigger multidrug-mediated resistance in OC cell lines. MDS bind to the colchicine site of tubulin, disrupting the microtubule network and causing antiproliferative and cytotoxic effects. In this work, a novel microtubule-destabilizing agent (PILA9) was synthetized and characterized. This compound also inhibited OC cell proliferation and induced G2/M cell cycle arrest and apoptosis. Interestingly, PILA9 was significantly more cytotoxic than MDS. Here, we also analyzed the effect of these microtubule-destabilizing agents (MDA) in combination with Panobinostat, a pan-histone deacetylase inhibitor. We found that Panobinostat synergistically enhanced MDA-cytotoxicity. Mechanistically, we observed that Panobinostat and MDA induced α-tubulin acetylation and that the combination of both agents enhanced this effect, which could be related to the observed synergy. Altogether, our results suggest that MDA/Panobinostat combinations could represent new therapeutic strategies against OC.

Perceptions of QOL among caregivers of Mexican ancestry of adults with advanced cancer.

PURPOSE: There is a substantial gap in the literature about the perceptions of QOL of caregivers of Mexican ancestry. This qualitative study explores the role of culture on the perceptions of QOL of this understudied population. METHODS: Twenty caregivers providing care to adults with advanced cancer were interviewed. Thematic analysis identified several themes for each domain of QOL, including physical, psychological, social, and spiritual domains and the role of culture. RESULTS: Cultural background influenced all of the QOL domains. There was a tremendous synergy across domains of physical, psychological, social, and spiritual well-being. Extended family and religious beliefs, life experiences, and culture were important components of QOL for these caregivers. Cultural expectations influenced role functioning and caregiver burden. CONCLUSION: This study informs our understanding of the role of culture on perceptions of QOL. Future investigations should be conducted with other Latino subgroups to describe QOL and to determine the role of culture on perceived QOL. Interventions should be specifically designed to improve caregivers' QOL and to reduce the burden of cancer in this underserved population.

The cancer caregiving experience of caregivers of Mexican ancestry.

The act of providing care may be the same in all ethnic groups, but the way caregiving is defined by family members is influenced by cultural values and beliefs. This study describes the caregiving experience and challenges of caregivers of Mexican ancestry. Qualitative interviews of 20 family caregivers and thematic analysis of transcribed audiotapes identified four themes that characterized their caregiving experience. These themes include an emphasis on family values, a strong commitment to care, difficulties dealing with everyday life realities, and a reliance on spirituality, all of which added to the meaningfulness and burden of caregiving. Further investigation within a cultural context is warranted in the development of interventions and programs to better assist caregivers in coping with the challenges of providing cancer care.

Barriers to treatment in patients with locally advanced breast cancer.

Delays between presentation and treatment could have a significant effect on breast cancer mortality. The authors hypothesized that patient, physician, and system barriers are all responsible for treatment delays. Therefore, a study was conducted to define prevalent barriers to treatment from the patient's perspective. A modified 43-item Likert-scale questionnaire was administered to patients with clinical stage III locally advanced breast cancer (LABC) who had experienced a delay in treatment of 3 months or more. Between October 2008 and January 2010, 153 patients presented with LABC; 43 patients (28.1%) met eligibility, and 40 completed the questionnaire. Among the patient barriers reported, 38% of patients delayed care for fear of losing their breast and 47% awaited previously scheduled routine appointments instead of seeking care. Among the physician barriers reported, 20% of physicians of initial contact did not believe the breast lump/symptom was related to cancer and 15% did not believe it needed a biopsy. Among the system barriers reported, the most prevalent were delays in performing diagnostic tests and obtaining insurance authorization for tests, treatment, or physician visits. Substantial delays were seen in 28.1% of patients from presentation to when they sought therapy at City of Hope Comprehensive Cancer Center. The high prevalence of patient barriers versus physician/system barriers suggests that increased educational efforts for patients and health care professionals are needed.

Family caregiver burden, skills preparedness, and quality of life in non-small cell lung cancer.

PURPOSE/OBJECTIVES: To describe burden, skills preparedness, and quality of life (QOL) for caregivers of patients with non-small cell lung cancer (NSCLC), and describe how the findings informed the development of a caregiver palliative care intervention that aims to reduce caregiver burden, improve caregiving skills, and promote self-care. DESIGN: Descriptive, longitudinal. SETTING: A National Cancer Institute-designated comprehensive cancer center in southern California. SAMPLE: 163 family members or friends aged 18 years or older and identified by patients as being a caregiver. METHODS: All eligible caregivers were approached by advanced practice nurses during a regularly scheduled patient clinic visit. Informed consent was obtained prior to study participation. Outcome measures were completed at baseline and repeated at 7, 12, 18, and 24 weeks. Descriptive statistics were computed for all variables, and one-way repeated-measures analysis of variance was used to test for change over time for all predictor and outcome variables. MAIN RESEARCH VARIABLES: Caregiver burden, skills preparedness, psychological distress, and QOL. FINDINGS: Caregivers were highly functional. Caregiver burden related to subjective demands increased significantly over time. Perceived skills preparedness was high at baseline but decreased over time. Psychological distress was moderate but increased in the study period. Overall QOL was moderate at baseline and decreased significantly over time. Psychological well-being had the worst QOL score. CONCLUSIONS: Caregivers experienced high levels of caregiver burden and reported deteriorations in psychological well-being and overall QOL. IMPLICATIONS FOR NURSING: Oncology nurses need to ensure that caregivers receive information that supports the caregiving role throughout the cancer trajectory. KNOWLEDGE TRANSLATION: Although family caregivers are profoundly impacted by a loved one's lung cancer diagnosis, the literature about caregiver burden, skills preparedness, and QOL is limited. Current evidence suggests that family caregivers can be negatively impacted by a loved one's cancer diagnosis. Caregiver-specific support interventions are needed to eliminate the burden of caregiving in lung cancer.

Survivorship education for Latina breast cancer survivors: Empowering Survivors through education.

OBJECTIVES: Nueva Luz is an English and Spanish quality of life (QOL) intervention developed to address the educational needs of Latina breast cancer survivors and provide strategies to assist in their transition into survivorship. METHODS: A qualitative approach was used to evaluate the English and Spanish educational intervention (Nueva Luz). A purposive sample of eight Latina breast cancer survivors was selected from the group who received the intervention to participate in a digitally recorded interview. Data was analyzed using thematic analysis. RESULTS: Findings provide evidence that the one-on-one tailored approach is a feasible and acceptable method of providing a bilingual psychosocial intervention. The provision of printed bilingual information along with the verbal instruction from a bilingual and culturally competent health care provider can be effective in helping Latina breast cancer survivor's transition successfully into survivorship, improve QOL and contribute to better patient outcomes. CONCLUSIONS: The study informs our understanding of the cultural context in patient education content and delivery of psychosocial interventions. The findings may also have relevance for other ethnic minority cancer survivors.

Impact of a bilingual education intervention on the quality of life of Latina breast cancer survivors.

PURPOSE/OBJECTIVES: To test the effectiveness of a bilingual education intervention to improve the quality of life (QOL) of Latina breast cancer survivors (BCSs) after completing primary treatment for breast cancer. DESIGN: A two-group prospective, longitudinal, randomized, controlled trial. SETTING: An ambulatory-care setting of a designated comprehensive cancer center in southern California. SAMPLE: 52 English- and Spanish-speaking Latina BCSs. METHODS: Women were randomly assigned to the experimental or attention control group and completed measures of QOL, uncertainty, distress, and acculturation at baseline, and at three and six months postintervention. MAIN RESEARCH VARIABLES: QOL, uncertainty, and distress. FINDINGS: After controlling for acculturation, the four dimensions of QOL increased slightly in the groups or remained unchanged without significant group-by-time interaction. The social and psychological well-being subscales had the lowest scores, followed by physical and spiritual well-being. Although the group-by-time interaction was not statistically significant, the post-hoc difference for total QOL between time 2 and time 3 in the experimental group approached significance, with a slight increase in total QOL. CONCLUSIONS: Latina BCSs have multiple survivorship and QOL concerns that might put them at risk for poor QOL. IMPLICATIONS FOR NURSING: More culturally congruent intervention studies are needed to address the paucity of intervention research with Latina BCS. KNOWLEDGE TRANSLATION: Core values must be incorporated in the development of health education programs. Those programs also should be linguistically appropriate and available to non-English-speaking Latinas. In this way, the informational and supportive needs of all BCSs can be met.

Enhancing the social well-being of family caregivers.

OBJECTIVES: To provide an overview of key issues and resources useful for oncology professionals to support the social well-being of patients and their families. A caregiver narrative highlights examples of the importance of addressing the social impact of illness. DATA SOURCES: Review of the literature and Web sites related to social well-being of oncology patients and families. CONCLUSION: Culture influences social well-being and impacts caregiving across the life span. Coping with cancer creates a myriad of social implications with potentially significant impacts on communication; sexuality, intimacy and sexual expression; education, finances, work, and leisure. IMPLICATIONS FOR NURSING PRACTICE: Nurses spend the greatest amount of time with patients and their families and therefore have an especially important role in identifying and addressing social needs. An interdisciplinary approach to care that includes the assessment of those at high risk and family meetings increases opportunities to address the complex multidimensional social concerns associated with oncology care.

Surgical treatment differences among Latina and African American breast cancer survivors.

PURPOSE/OBJECTIVES: To describe breast cancer treatment choices from the perspectives of Latina and African American breast cancer survivors. DESIGN: An interdisciplinary team conducted a mixed-methods study of women treated for stages I-IV breast cancer. SETTING: Participants' homes in metropolitan areas. SAMPLE: 39 participants in three groups: monolingual Spanish-speaking Latinas (n = 15), English-speaking Latinas (n = 15), and African American women (n = 9). METHODS: Individual participant interviews were conducted by racially and linguistically matched nurse researchers, and sociodemographic data were collected. Content and matrix analysis methods were used. MAIN RESEARCH VARIABLES: Perceptions of breast cancer care. FINDINGS: High rates of mastectomy were noted for early-stage treatment (stage I or II). Among the participants diagnosed with early-stage breast cancer, the majority of English-speaking Latinas (n = 9) and African American women (n = 4) received a mastectomy. However, the majority of the Spanish-speaking Latina group (n = 5) received breast-conserving surgery. Four factors influenced the choice of mastectomy over lumpectomy across the three groups: clinical indicators, fear of recurrence, avoidance of adjuvant side effects, and perceived favorable survival outcomes. Spanish-speaking Latinas were more likely to rely on physician treatment recommendations, and the other two groups used a shared decision-making style. CONCLUSIONS: Additional study is needed to understand how women select and integrate treatment information with the recommendations they receive from healthcare providers. Among the Spanish-speaking Latina group, limited English proficiency, the use of translators in explaining treatment options, and a lack of available educational materials in Spanish are factors that influenced reliance on physician recommendations. IMPLICATIONS FOR NURSING: Oncology nurses were notably absent in supporting the women's treatment decision making. Advanced practice oncology nurses, coupled with language-appropriate educational resources, may provide essential guidance in clarifying surgical treatment choices for breast cancer among culturally and linguistically diverse populations.

The quality of life of patients with malignant gliomas and their caregivers.

The grim prognosis that accompanies a diagnosis of a malignant glioma affects quality of life (QOL) as patients attempt to adapt to overwhelming losses. Caregivers also experience negative changes in QOL as responsibilities grow. This pilot study measured the QOL of patients with malignant gliomas prior to tumor progression and the QOL of their caregivers. It examined negative and positive factors that impacted the QOL while highlighting positive factors often overlooked in brain tumor QOL research. Standardized QOL questionnaires and focus groups were utilized. Patients experienced distress in the domains of physical, psychological, and social QOL but in all four of the QOL domains there were also positive outcomes. Caregiver data demonstrated mostly positive outcomes in the four QOL domains except for loved one's declining health and fear that the loved one would die.

Symptom concerns and quality of life in hepatobiliary cancers.

PURPOSE/OBJECTIVES: To describe the symptom concerns of patients with hepatocellular carcinoma (HCC) and pancreatic cancer and explore the effect of symptoms on patients' quality of life (QOL). DESIGN: Descriptive, longitudinal study. SETTING: Ambulatory clinics of a comprehensive cancer center. SAMPLE: 45 patients actively receiving treatment for either HCC or pancreatic cancer. METHODS: Patients were followed from baseline for three months, with outcome measures repeated monthly. Outcome measures included the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and the Functional Assessment of Chronic Illness Therapy-Spirituality Subscale (FACIT-Sp-12). Descriptive analysis of demographic, treatment, and symptom data was conducted, followed by two-way repeated measures analysis of variance of FACT-Hep and FACIT-Sp-12 scale scores by diagnosis and treatment type. MAIN RESEARCH VARIABLES: Symptoms, QOL. FINDINGS: Overall QOL is poor in patients with hepatobiliary cancer, and this trend continues over time. Symptoms such as abdominal pain, fatigue, weight loss, and poor appetite commonly are reported in this population. CONCLUSIONS: Patients with hepatobiliary cancer suffer from multiple symptoms that may have a negative affect on overall QOL. Specific QOL domains, such as physical and functional well-being, are of particular concern for patients. IMPLICATIONS FOR NURSING: The identification of specific symptom and QOL concerns in hepatobiliary cancers will enhance clinical care and aid in the future development of multidisciplinary interventions for this understudied cancer population.

Distress and quality of life concerns of family caregivers of patients undergoing palliative surgery.

There has been limited research in the field of palliative care and even far less focus on the area of palliative surgery. Although patient needs are paramount, family caregivers require information and support at the time surrounding surgery for advanced disease. The aim of this prospective cohort study of family caregivers of patients with advanced malignancies was to measure the impact of palliative surgery on dimensions of quality of life (QOL) for these family members. Family caregivers completed assessment tools preoperatively and at approximately 3 weeks and 2 and 3 months postoperatively. Parameters of physical, psychological, social, and spiritual QOL were measured on a scale of 0 (poor) to 10 (good) using the City of Hope QOL-Family instrument. Caregivers recorded their general distress on the Distress Thermometer using a scale of 0 (none) to 10 (severe). Analysis of the data revealed that family caregivers had disruptions similar to patients in physical, psychological, social, and spiritual dimensions of QOL. Findings suggest that caregivers should be assessed for distress and QOL concerns both before and after surgery for patients with advanced malignancies. Although caregiver concerns cannot always be eradicated, resources and interventions to support family caregivers are vital to improving QOL.

Challenges and strategies in recruitment of ethnically diverse populations for cancer nursing research.

PURPOSE/OBJECTIVES: To describe common barriers, identify challenges for researchers, and provide strategies for recruitment and retention of ethnic minority groups for cancer nursing research. DATA SOURCES: Computerized search of databases, published articles, abstracts, master's theses, and doctoral dissertations. DATA SYNTHESIS: Social, economic, and cultural factors present challenges to recruitment of minorities into research. Knowing the culture of the target population, developing trust, engaging the community, and using tailored materials are strategies for recruitment and retention of minorities. CONCLUSIONS: Knowledge of potential barriers and challenges to research with diverse populations provides the foundation for the development of strategies for successful recruitment of minorities in cancer nursing research. IMPLICATIONS FOR NURSING: Increasing ethnic minorities in research will generate knowledge that will contribute to culturally competent cancer care.

Surgical palliation of advanced gastrointestinal tumors.

Patients with advanced gastrointestinal tumors suffer a spectrum of progressive symptoms that reduce their quality of life (QOL). Operative palliative strategies seeking to improve QOL and decrease symptom burden are poorly studied. This study seeks to measure the effect of operations on symptoms and QOL in patients with advanced gastrointestinal malignancies. Patients undergoing World Health Organization (WHO)-defined palliative operations for gastrointestinal cancers were prospectively followed with monthly QOL and Distress Thermometer surveys until 6 months post-operatively. Comparisons were made between preoperative and 3-month postoperative data. Parameters of physical, psychological, social, and spiritual QOL were measured on a scale of 0 (worst) to 5 (best). Frequency of occurrence and degree of distress caused by that specific symptom were scored from 0 (rarely/not at all) to 5 (most of the time/severely). Thirty-five patients had gastrointestinal cancer. The median age was 55.3 years. The most common symptoms were pain and obstruction. Thirty-three operations were abdominal. Ultimately, 34 patients (97%) were discharged home. When preoperative data were compared to 3 months postoperative, the frequency of the primary symptom improved by 2.22 (p = 0.001) and the distress it caused decreased by 1.82 (p = 0.004). Physical QOL decreased by 0.61 (p = 0.009), psychological QOL decreased by 0.50 (p = 0.015), social QOL decreased by 0.48 (p = 0.017), spiritual QOL decreased by 0.42 (p = 0.008), and overall QOL decreased by 0.50 (p = 0.012). Because of the unrelenting nature of gastrointestinal tumors, QOL over time will inevitably decrease. Palliative operations effectively improve symptom frequency and distress without greatly affecting the expected decline in QOL and its parameters.

Management of pain and nausea in outpatient surgery.

The cost associated with surgical procedures has been dramatically decreased by the ability to perform these procedures on an outpatient basis. Pain and nausea, two common symptoms after anesthesia and surgical procedures, are among the greatest concerns for patients and their family members. As a result of the distress and sequelae associated with these symptoms, clinicians have attempted to determine the optimal intraoperative and postoperative symptom management for patients. The purpose of this quality improvement project was to describe the incidence of these symptoms and their management in patients who underwent planned outpatient surgical procedures in a cancer center. A sample of 39 patients were accrued at a comprehensive cancer center over a 3-month period. Data were collected at three specific time points (i.e., preoperatively, at 24 hours and at 7 days postoperatively). Postoperative pain and nausea were generally well managed, but improvement was needed in preoperative patient teaching, including the topics of drug and nondrug interventions. The methods used in this project have potential application for the measurement of other clinical outcomes after outpatient surgical procedures.

Perspectives on the impact of ovarian cancer: women's views of quality of life.

PURPOSE/OBJECTIVES: To describe quality-of-life (QOL) concerns particular to women with ovarian cancer and to examine whether subgroups of patients with ovarian cancer have significantly different QOL concerns. DESIGN: Mailed survey. SAMPLE: Readership of an ovarian cancer newsletter. METHODS: A total of 1,383 surveys were received in response to the survey's inclusion in the November 2002 issue of Conversations! The International Newsletter for Those Fighting Ovarian Cancer, a monthly newsletter circulated to 3,300 women with ovarian cancer (response rate = 42%). Women were asked to complete the 45-item City of Hope QOL Ovarian Cancer Tool (QOL-OVCA) and a short demographic questionnaire. MAIN RESEARCH VARIABLES: Patients' QOL-OVCA scores were compared across six independent variables, including disease status, age at diagnosis, stage at diagnosis, marital status, household income, and use of alternative therapy, controlling for survival time. FINDINGS: Ovarian cancer survivors reported significant QOL concerns across dimensions of physical, psychological, social, and spiritual well-being. CONCLUSIONS: Patients with ovarian cancer experience particular QOL concerns requiring support. Future research is needed to describe the needs of survivors in more diverse populations and to develop and test interventions that can address these QOL concerns. IMPLICATIONS FOR NURSING: Women with ovarian cancer experience QOL concerns common to other patients with cancer and some that are particular to ovarian cancer. Nurses should assess for and aggressively address these QOL concerns.

Concerns of family caregivers of patients with cancer facing palliative surgery for advanced malignancies.

PURPOSE/OBJECTIVES: To describe the concerns of family caregivers of patients undergoing palliative surgeries for advanced malignancies. DESIGN: Descriptive study with repeated measures. SETTING: A National Cancer Institute-designated Comprehensive Cancer Center in the western United States. SAMPLE: Family caregivers (N = 45) of patients with cancer. METHODS: Family caregivers were assessed prior to planned palliative surgery and at two weeks and six weeks postsurgery. Quantitative assessment of caregiver quality of life (QOL) occurred at each interval. A subset of nine caregivers also participated in a structured interview presurgery and at two weeks postsurgery. MAIN RESEARCH VARIABLES: Caregiver concerns, QOL, decision making. FINDINGS: Family caregivers have important QOL concerns and needs for support before and after surgery for advanced disease. Psychological issues were most pronounced, and common concerns included uncertainty, fears regarding the future, and loss. Family caregivers have concerns about surgical risks and care after surgery and voiced recognition of the declining status of patients. CONCLUSIONS: Surgery is an important component of palliative care and profoundly impacts family caregivers of patients with cancer. The needs of family caregivers are multiple and complex, requiring ongoing assessment to provide interventions that help them cope and ultimately improve their QOL. This important topic requires further research and clinical attention. IMPLICATIONS FOR NURSING: Findings suggest that family caregivers experience their own trajectory during the course of their loved ones' cancer, with surgery being a part of the course. This includes their profound emotions that may swing like a pendulum from one minute to the next. Nurses need to assess family caregivers in addition to patients to provide support and resources that will help increase caregivers' QOL.