Pregnancy-associated takotsubo cardiomyopathy hospitalizations in the United States.

Takotsubo cardiomyopathy (TCM) is most common not only in postmenopausal women aged ≥50 yr but also in pregnant individuals. However, there are no national estimates on the prevalence, timing of occurrence, correlates, and outcomes of pregnancy-associated TCM. Using the Nationwide Inpatient Sample (NIS: 2016-2020), we describe rates of pregnancy-associated TCM hospitalizations among 13- to 49-yr-old pregnant individuals in the United States by selected demographic, behavioral, hospital, and clinical characteristics. Joinpoint regression was used to describe the annual average percent change of pregnancy-associated TCM hospitalizations. Survey logistic regression was used to measure the association of pregnancy-associated TCM hospitalizations with maternal outcomes. Of the 19,754,535 pregnancy-associated hospitalizations, 590 were TCM associated. The overall trend in pregnancy-associated TCM hospitalizations remained stable during the study period. The majority of TCM occurred during the postpartum, followed by antepartum and delivery-associated hospitalizations. When compared with pregnancy hospitalizations without TCM, those with TCM were more likely to be over the age of 35 yr and use tobacco and opioids. Comorbidities during TCM-associated pregnancy hospitalizations included heart failure, coronary artery disease, hemorrhagic stroke, and hypertension. After controlling for potential confounders, the odds of pregnancy-associated TCM hospitalizations were 98.7 times [adjusted odds ratio (aOR) = 98.66, 95% confidence interval (CI) 31.23-311.64] and 14.7 times (aOR = 14.75, 95% CI 9.99-21.76) higher for experiencing in-hospital mortality and a prolonged hospital stay, respectively, than those without TCM. Although rare, pregnancy-associated TCM hospitalization is more likely to occur during the postpartum period and is associated with in-hospital mortality and prolonged hospital stay.NEW & NOTEWORTHY Although rare, pregnancy-associated takotsubo cardiomyopathy hospitalizations are more likely to occur during the postpartum period and are associated with in-hospital mortality and prolonged hospital stay.

A systematic review of interventions for family caregivers who care for patients with advanced cancer at home.

OBJECTIVE: To examine the characteristics of interventions to support family caregivers of patients with advanced cancer. METHODS: Five databases (CINAHL, Medline, PsycINFO, Web of Science, and the Cochrane Library) were searched for English language articles of intervention studies utilizing randomized controlled trials or quasi-experimental designs, reporting caregiver-related outcomes of interventions for family caregivers caring for patients with advanced cancer at home. RESULTS: A total of 11 studies met the inclusion criteria. Based on these studies, the types of interventions were categorized into psychosocial, educational, or both. The characteristics of interventions varied. Most interventions demonstrated statistically significant results of reducing psychological distress and caregiving burden and improving quality of life, self-efficacy, and competence for caregiving. However, there was inconsistency in the use of measures. CONCLUSIONS: Most studies showed positive effects of the interventions on caregiver-specific outcomes, yet direct comparisons of the effectiveness were limited. There is a lack of research aimed to support family caregivers' physical health. PRACTICE IMPLICATIONS: Given caregivers' needs to maintain their wellbeing and the positive effects of support for them, research examining long-term efficacy of interventions and measuring objective health outcomes with rigorous quality of studies is still needed for better outcomes for family caregivers of patients with advanced cancer.

Quality of life among Korean gastrointestinal cancer survivors.

PURPOSE: The number of gastrointestinal (GI) cancer survivors has been steadily increasing owing to early diagnosis and improved cancer treatment outcomes. The quality of life (QoL) of cancer survivors can provide distinct prognostic information and represent their functioning. This study aimed to investigate the levels of symptoms, psychological distress, and QoL of GI cancer survivors, and identify factors associated with QoL. METHOD: A cross-sectional survey was conducted among 145 survivors of gastric or colorectal cancer in a university-affiliated hospital, Seoul, South Korea. The questionnaire consisted of the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module, Distress Thermometer, and brief version of the World Health Organization Quality of Life Assessment Instrument. Quantile regression was used to assess the associated factors of QoL. The 10th, 25th, 50th, 75th, and 90th conditional quantiles were considered. RESULTS: The most common symptoms were fatigue (24.9%), numbness or tingling (17.2%), feeling bloated (17.2%), dry mouth (15.9%), and difficulty remembering (11.8%). Thirty-two percent (47/145) of the participants reported severe distress. A level of symptoms was significantly associated in the 10th and 25th quantiles, representing poor QoL. Economic burden was a significant influencing factor in all quantiles. CONCLUSION: Our results indicate that high burden from symptoms might be associated with lower QoL in GI cancer survivors, and higher economic burden from cancer treatment was associated with lower QoL. These results suggest that symptom management and support for economic difficulties should be included in the strategies to enhance the QoL of GI cancer survivors.

Peroxiredoxin I and II inhibit H2O2-induced cell death in MCF-7 cell lines.

Apoptosis is known to be induced by direct oxidative damage due to oxygen-free radicals or hydrogen peroxide or by their generation in cells by the actions of injurious agents. Together with glutathione peroxidase and catalase, peroxiredoxin (Prx) enzymes play an important role in eliminating peroxides generated during metabolism. We investigated the role of Prx enzymes during cellular response to oxidative stress. Using Prx isoforms-specific antibodies, we investigated the presence of Prx isoforms by immunoblot analysis in cell lysates of the MCF-7 breast cancer cell line. Treatment of MCF-7 with hydrogen peroxide (H2O2) resulted in the dose-dependent expressions of Prx I and II at the protein and mRNA levels. To investigate the physiologic relevance of the Prx I and II expressions induced by H2O2, we compared the survivals of MCF10A normal breast cell line and MCF-7 breast cancer cell line following exposure to H2O2. The treatment of MCF10A with H2O2 resulted in rapid cell death, whereas MCF-7 was resistant to H2O2. In addition, we found that Prx I and II transfection enabled MCF10A cells to resist H2O2-induced cell death. These findings suggest that Prx I and II have important functions as inhibitors of cell death during cellular response to oxidative stress.

BetaPix-a enhances the activity of phospholipase Cgamma1 by binding SH3 domain in breast cancer.

Phospholipase C-gamma1 (PLCgamma1) plays a critical role in cell growth and proliferation by generating the second messengers, diacylglycerol and 1, 4, 5-inositol triphosphate. To investigate the roles of Src homology domain 2 and domain 3 of PLCgamma1 in PLCgamma1-mediated cell signaling, we characterized some proteins binding to these domains in the MCF7 and MDA-MB-231 breast cancer cell lines. Of the several proteins that bind to glutathione-S-transferase-SH2/SH2/SH3, we identified an 85 kDa protein that binds to the SH3 domain of PLCgamma1 as the guanine nucleotide exchange factor, p21-activated protein kinase-interacting exchange factor-a (betaPix-a). BetaPix-a co-immunoprecipitated with PLCgamma1 in breast cancer tissues extracts and in MCF7 and MDA-MB-231 cell extracts. In addition, PDGF-stimulated PLCgamma1 activity was elevated in betaPix-a-overexpressing NIH3T3 cells. Our results suggest that betaPix-a binds to the Src homology domain 3 of PLCgamma1 and promotes tumor growth in breast cancer by enhancing the activity PLCgamma1.

Phospholipase C-protein kinase C mediated phospholipase D activation pathway is involved in tamoxifen induced apoptosis.

Tamoxifen (TAM) is the endocrine therapeutic agent the most widely used in the treatment of breast cancer, and it operates primarily through the induction of apoptosis. In this study, we attempted to elucidate the non-ER mediated mechanism behind TAM treatment, involving the phospholipase C-protein kinase C (PLC-PKC) mediated phospholipase D (PLD) activation pathway, using multimodality methods. In TAM treated MCF7 cells, the PLC and PLD protein and mRNA levels increased. Phosphatidylethanol (PEt) and diacylglycerol (DAG) generation also increased, showing increased activity of PLD and PLCgamma1. Translocation of PKCalpha, from cytosol to membrane, was observed in TAM treated cells. By showing that both PKC and PLC inhibitors could reduce the effects of TAM-induced PLD activation, we confirmed the role of PKC and PLC as upstream regulators of PLD. Finally, we demonstrated that TAM treatment reduced the viability of MCF7 cells and brought about rapid cell death. From these results, we confirmed the hypothesis that TAM induces apoptosis in breast cancer cells, and that the signal transduction pathway, involving PLD, PLC, and PKC, constitutes one of the possible mechanisms underlying the non-ER mediated effects associated with TAM.

Overexpression of betaPix-a in human breast cancer tissues.

Pak interacting exchange factor (betaPix) is a recently cloned protein that contains a multidomain with many potential binding sites and is known to be involved in the regulation of Cdc42/Rac GTPases and Pak kinase activity. These domains of betaPix appear to play a critical role in the regulation of the cytoskeletal organization. The overexpression of betaPix enhances the activation of p38, which is thought to be an important downstream effector of the Rho GTPase family (Rac, Cdc42), which are involved in increased membrane ruffling and cell motility. This increase of cell mobility is an important feature of cancer invasion. We examined the expression of betaPix-a in human breast cancer tissues and adjacent normal tissues obtained from 39 breast cancer patients. Immunoblot analysis and RT-PCR revealed that betaPix-a expression was significantly increased in 37 of the 39 breast cancer tissues (94.9%) versus normal breast tissues. Immunohistochemical analysis showed that breast cancer tissues have consistently stronger immunoreactivity to betaPix-a antibodies than normal tissues. betaPix-a overexpression was inversely associated with extensive intraductal component (P<0.001). In conclusion, betaPix-a expression was found to be higher in human breast cancer tissues than in normal breast tissues, which implies a role for betaPix-a in human breast tumorigenesis. We suggest that betaPix-a may be a useful marker of malignant disease in the breast.

Full sequencing analysis of estrogen receptor-alpha gene polymorphism and its association with breast cancer risk.

BACKGROUND: The estrogen receptor plays a critical role in breast cancer development and progression. So the genetic polymorphism of ER-alpha gene could affect cancer risk and phenotype. MATERIALS AND METHODS: We fully sequenced the ER-alpha gene to investigate its single nucleotide polymorphisms (SNPs) in 100 breast cancer patients and 100 controls. RESULTS: Six novel polymorphism in the control and 11 in cancer patients were found. The G/G genotype at C975 G and A/A genotype at G1782 A had a protective effect against breast cancer when compared to other genotypes (OR = 0.3 and 0.3, respectively). 975G allele was associated inversely with the p53 expression and positively with the bcl-2 expression in cancer with borderline significance. Combining this result with our previous study, these associations became more significant (p = 0.005 and 0.019, respectively). CONCLUSION: Polymorphisms in ER-alpha gene can affect the breast cancer susceptibility and may be related to other protein expression, such as p53 and bcl-2.

Identification of angiogenesis in primary breast carcinoma according to the image analysis.

Tumor angiogenesis may be an independent prognostic factor for breast cancer survival. However, we can get the angiogenic property of the breast cancer only after the removal of breast tissue. To get this information before surgical resection of the tumor, we evaluated 29 breast carcinoma patients with Tc-99m MIBI scintimammography and power Doppler ultrasound (US) with a microbubble contrast agent preoperatively and compare their results with intratumoral microvessel density (IMD) and reverse transcriptase-polymerase chain reaction (RT-PCR) of VEGF mRNA. IMD was well correlated with VEGF121 (r = 0.220, P = 0.024) and VEGF165 (r = 0.419, P = 0.046) mRNA level of the tumor. Power Doppler US grading of the tumor is well correlated with IMD (r = 0.552, P = 0.033). However, early uptake and washout index calculated from Tc-99m MIBI scintimammography showed no correlation with IMD or VEGF mRNA level, while washout index was inversely correlated with power Doppler US grading (r = -0.945, P = 0.001). In conclusion, the preoperative evaluation of breast cancer with power Doppler US with a microbubble contrast agent could predict tumor angiogenesis. Tc-99m MIBI scintimammography needs further study to use it as an image analysis for angiogenesis.