Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC. PATIENTS AND METHODS: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed. RESULTS: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively. CONCLUSIONS: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

Differential effects of aquatic anaesthetics on the pharmacokinetics of antibiotics: Examples using florfenicol in Nile tilapia (Oreochromis niloticus).

Anaesthetics are commonly applied in pharmacokinetic (PK) studies to assure smooth handling of experimental procedures or to promote animal welfare. However, the influence of anaesthetics on the PK of co-administered drug is generally unknown but assumes ignorable. The goal of the study was to investigate the effect of tricaine methanesulfonate (MS-222), 2-phenoxyethanol (2-PE) and eugenol (EUG) on the PK of florfenicol (FF) in Nile tilapia. Twenty-eight fish were repeatedly exposed to 90 ppm EUG, 300 ppm MS-222 or 900 ppm 2-PE before FF oral administration (15 mg/kg) and each successive blood sampling. The serum concentration-time profiles were analysed by a 2-compartmental model, and the generated parameters in the control (without anaesthetic) and anaesthetic groups were statistically compared. The results demonstrated that the serum concentrations of each anaesthetic were similar at every FF sampling times (70 µg/ml for MS-222; 277 µg/ml for 2-PE; and 61 µg/ml for EUG). In comparison with the control group, the repeated use of MS-222 did not result in a statistical difference in most of the PK parameters. In contrast, the elimination half-lives of the 2-PE and EUG groups were significantly longer whereas the absorption and distribution half-lives of the 2-PE group were significantly shorter than the control, resulting in altered optimal dosages in the simulation modelling. Whether or not the numbers and extent of PK parameters change mitigate subsequent estimations of other PK-derived secondary values such as dosing regimen and withdrawal time remains to be elucidated, but the auxiliary use of anaesthetics in PK studies should not assume uninfluential.

Gaussian Thermal Operations and The Limits of Algorithmic Cooling.

The study of thermal operations allows one to investigate the ultimate possibilities of quantum states and of nanoscale thermal machines. Whilst fairly general, these results typically do not apply to continuous variable systems and do not take into account that, in many practically relevant settings, system-environment interactions are effectively bilinear. Here we tackle these issues by focusing on Gaussian quantum states and channels. We provide a complete characterization of the most general Gaussian thermal operation acting on an arbitrary number of bosonic modes, which turn out to be all embeddable in a Markovian dynamics, and derive necessary and sufficient conditions for state transformations under such operations in the single-mode case, encompassing states with nonzero coherence in the energy eigenbasis (i.e., squeezed states). Our analysis leads to a no-go result for the technologically relevant task of algorithmic cooling: We show that it is impossible to reduce the entropy of a system coupled to a Gaussian environment below its own or the environmental temperature, by means of a sequence of Gaussian thermal operations interspersed by arbitrary (even non-Gaussian) unitaries. These findings establish fundamental constraints on the usefulness of Gaussian resources for quantum thermodynamic processes.

Risk of gynaecological malignancies in cytologically atypical glandular cells: follow-up study of a nationwide screening population.

OBJECTIVE: To investigate the relationship between screening status, clinical characteristics and risk of gynaecological malignancies in women with a cytological diagnosis of atypical glandular cells (AGC). DESIGN: Prospective study of a screened population. POPULATION: Case series from nationwide screening population. METHODS: The 8281 women who were diagnosed with cytological AGC for the first time were divided into screened (5386 women) and unscreened (2895 cases) groups according to their screening status. Follow-up histological reports were analysed. MAIN OUTCOME MEASURES: Diagnosis of cervical, uterine, or ovarian cancers. RESULTS: Of the 323 women who developed gynaecological malignancies, 271 had invasive cervical cancers, 40 had uterine cancers and 12 had ovarian cancers, with a mean follow up of 1.9 years and 50 740 person-years. Previous screening status was a strong risk predictor of gynaecological malignancies (hazard ratio 1.69, P = 0.0027). Compared with the general screening population, women with a first diagnosis of cytological AGC had significantly increased ratios of developing gynaecological malignancies (17.85-fold for cervical cancer, 5.68-fold for uterine cancer, and 2.04-fold for ovarian cancer, P < 0.05). When compared with women aged <35 years, those in other age groups had a significantly higher risk of developing gynaecological cancers (age ≥60 years, hazard ratio 1.99, 95% CI 1.20-2.37, P = 0.016). CONCLUSIONS: Comprehensive evaluation for women with cytological AGC, including pelvic examination, ultrasonography, colposcopy, endocervical curettage, cervical biopsy and endometrial biopsy needs to be considered, especially for those with risk factors (i.e. >60 years old, lower educational status, previous Papanicolaou smear interval longer than 2 years, or no previous Papanicolaou smear).

Brain metastasis as a late manifestation of ovarian carcinoma.

This paper aims to evaluate the clinical characteristics of ovarian cancer patients with cerebral metastases. Ten ovarian cancer patients with brain metastases were retrospectively identified from a total of 539 ovarian cancer patients. Their characteristics before and at the time of diagnosis of cerebral metastases were analysed. The survival of them was also measured. Ten (1.9%) of the 539 ovarian cancer patients had brain metastases in the study period. Nine had stage III or IV tumours with either moderate or poor histological differentiation. The mean time from diagnosis of ovarian cancer to documentation of central nervous system metastasis was 24.3 months, which was 11.1 months if other sites of metastasis were involved before cerebral relapse. All of the patients with intra-cranial tumours suffered from associated neurological defects and relived by treatments. The median survival time after diagnosis of central nervous system involvement was 3 months. In this study, all ovarian cancer patients with cerebral metastases had clinical neurological symptoms. Physicians should pay more attention to ovarian cancer patients with neurological defects and arrange brain imaging studies for the early diagnosis of brain metastases and prompt management to improve quality of life.

Morphine-sparing effect by COX-1 inhibitor sustains analgesic function without compromising antigen-specific immunity and antitumor effect of naked DNA vaccine.

Morphine and ketorolac, two analgesics with different mechanisms, have been widely used in controlling cancer pain and postoperative pain in surgery. Our previous study revealed that morphine could suppress the anti-tumor effect of antigen-specific DNA vaccine. In this study, we further evaluated and compared another analgesic drug, ketorolac, with morphine for its analgesic functions and the antitumor immunities of antigen-specific DNA vaccine. We first observed that ketorolac-treated mice did not enhance tumorigenesis nor suppress the anti-tumor effects of antigen-specific (calreticulin linked to HPV16 E7) CRT/E7 DNA vaccine. We then demonstrated that ketorolac was less potent in inducing apoptosis of T lymphocytes and the generation of reactive oxygen species, in reducing mitochondrial membrane potentials, and leading to the activation of caspases 3 and 7 in T lymphocytes than morphine. When CRT/E7 DNA vaccinated mice treated with ketorolac, the declines of frequencies of E7-specific IFN-gamma-secreting CD8+ T cell precursors were slower in the morphine-treated group. CRT/E7 DNA vaccinated mice, treated with a mixture of morphine and ketorolac, could maintain the analgesic function without experiencing a decrease in the anti-tumor effects. CRT/E7 DNA vaccine with the opioid-sparing effect of ketorolac could provide potent anti-tumor effects and good analgesic function.

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects.

Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.

High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma.

The objective of this paper is to investigate the mesothelin expression level to the clinicopathological features, chemoresponse, and to the outcome of patients with epithelial ovarian carcinoma (EOC). Mesothelin mRNA was detected by real-time quantitative reverse-transcription PCR in 139 EOC patients. Clinical characteristics, histopathological items, responses to chemotherapy, progression-free survival (PFS), and overall survival (OS) were recorded. Tumours with advanced stages had higher mesothelin than those with early stages. The chemoresistant patients showed significantly higher mesothelin than did chemosensitive patients (2.81 vs 0.43, P<0.001), irrespective of optimal or suboptimal surgery in those with advanced stages. Highly expressed levels of mesothelin were an independent but poor prognostic factor in the PFS (2.03 (1.23-3.37) P=0.006) and OS (3.72 (1.64-8.45), P=0.002) of the 139 EOC patients in multivariate analysis. In addition, patients in advanced stages with highly expressed mesothelin also had significantly worse OS, regardless of whether they had undergone optimal (13.85 (1.76-125.60), P=0.013) or suboptimal (4.47 (1.83-10.88), P=0.001) debulking surgery in multivariate analysis. Out results provide new evidence that mesothelin expression is associated with chemoresistance and with shorter disease-free survival and worse OS of patients with EOC.

Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences.

BACKGROUND: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. RESULTS: The invasive cancer incidence decreased by 47.8% during 1995-2006. The carcinoma in situ incidence increased 1.7-fold during 1995-2000, and decreased by 19.6% during 2000-2006. CONCLUSION: The Taiwan national programme has significantly decreased invasive cervical cancer.

Biostabilization assessment of MSW co-disposed with MSWI fly ash in anaerobic bioreactors.

Municipal solid waste incinerator (MSWI) fly ash has been examined for possible use as landfill interim cover. For this aim, three anaerobic bioreactors, 1.2m high and 0.2m in diameter, were used to assess the co-digestion or co-disposal performance of MSW and MSWI fly ash. Two bioreactors contained ratios of 10 and 20 g fly ash per liter of MSW (or 0.2 and 0.4 g g(-1) VS, that is, 0.2 and 0.4 g fly ash per gram volatile solids (VS) of MSW). The remaining bioreactor was used as control, without fly ash addition. The results showed that gas production rate was enhanced by the appropriate addition of MSWI fly ash, with a rate of approximately 6.5l day(-1)kg(-1)VS at peak production in the ash-added bioreactors, compared to approximately 4l day(-1)kg(-1)VS in control. Conductivity, alkali metals and VS in leachate were higher in the fly ash-added bioreactors compared to control. The results show that MSW decomposition was maintained throughout at near-neutral pH and might be improved by release of alkali and trace metals from fly ash. Heavy metals exerted no inhibitory effect on MSW digestion in all three bioreactors. These phenomena indicate that proper amounts of MSWI fly ash, co-disposed or co-digested with MSW, could facilitate bacterial activity, digestion efficiency and gas production rates.

Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism.

A novel method for generating an antigen-specific cancer vaccine and immunotherapy has emerged using a DNA vaccine. However, antigen-presenting cells (APCs) have a limited life span, which hinders their long-term ability to prime antigen-specific T cells. Connective tissue growth factor (CTGF) has a role in cell survival. This study explored the intradermal administration of DNA encoding CTGF with a model tumor antigen, human papilloma virus type 16 E7. Mice vaccinated with CTGF/E7 DNA exhibited a dramatic increase in E7-specific CD4(+) and CD8(+) T-cell precursors. They also showed an impressive antitumor effect against E7-expressing tumors compared with mice vaccinated with the wild-type E7 DNA. The delivery of DNA encoding CTGF and E7 or CTGF alone could prolong the survival of transduced dendritic cells (DCs) in vivo. In addition, CTGF/E7-transduced DCs could enhance a higher number of E7-specific CD8(+) T cells than E7-transduced DCs. By prolonging the survival of APCs, DNA vaccine encoding CTGF linked to a tumor antigen represents an innovative approach to enhance DNA vaccine potency and holds promise for cancer prophylaxis and immunotherapy.

Synchronous primary cancers of the endometrium and ovary.

Simultaneous detection of malignancy in the endometrium and ovary represents an uncommon event. The objective of the study was to clarify the possible factors that influenced on the survival. From 1977 to 2005, totally 27 patients fulfilled the criteria and were included in the study. The medical records and the pathologic reports were reviewed. The histologic determination was followed by the World Health Organization Committee classification, and cancer stage was based on the staging system of the FIGO. The Kaplan-Meier survival analyses were generated and compared by the log-rank test. The incidence of synchronous primary endometrial and ovarian cancers was 3.3% in patients with endometrial cancer and 2.7% in patients with ovarian cancer. The mean survival in the group of similar histology (n= 15) was 63 months, and 48 months in the group of dissimilar histology (n= 12) (P= 0.63). The mean survival in the group of early stage (n= 21) was 68 months and 15 months in the group of advanced stage (n= 6) with statistic significance (P= 0.0003). However, the impact of adjuvant therapy on survival did not reach statistic significance (P= 0.15 for chemotherapy; P= 0.69 for radiotherapy). We conclude that the majority of the patients belonged to concordant endometrioid histology in endometrium and ovary, and it tends to be early stage and low grade with favorable prognosis. The stage had more significant influence on the survival than the histology. Adjuvant therapy should be given especially in patients with advanced stage although the optimal management remained to be determined.

Effective Decision-Making and Decisional Regret in Living Kidney Donors of Taiwan.

BACKGROUND: While most living kidney donors are satisfied with their decision and do not regret donating, few studies have been conducted on the determinants related to the effectiveness and regret of the decision. This study aims to explore the relationship between basic attributes, quality of life, positive affect, negative affect, effectiveness of decision-making, and regret in living kidney donors. METHODS: In this cross-sectional study, living kidney donors were recruited from urology and kidney transplant outpatient services. The structured questionnaire used to collect the data included the Positive and Negative Affect Schedule, Medical Outcomes Study 12-Item Short-Form Health Survey, Decision Conflict Scale, and Decision Regret Scale. RESULTS: The findings indicate that living donors with better health status, 24-hour creatinine clearance, physical health-related quality of life (HRQOL), and positive affect experienced greater feelings of effective decision-making. Moreover, women and donors with better physical HRQOL, positive affect, and decision effectiveness were less regretful about the decision of kidney donation. CONCLUSION: Health status, physical HRQOL, and positive affect are related to decision validity and regret of living donors. Therefore, clinical care providers should regularly assess the mood and health of living kidney donors. Furthermore, activities promoting their health should be encouraged, especially for men.

Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway.

This study is to investigate the molecular mechanism of radiation-enhanced cell invasiveness of hepatocellular carcinoma (HCC) correlating with clinical patients undergoing radiotherapy and subsequently developing metastasis. Three HCC cell lines (HepG2, Hep3B and Huh7) and normal hepatocyte cell line (CL-48) were irradiated with different doses. The effect of radiation on cell invasiveness was determined using the Boyden chamber assay. Radiation-enhanced invasion capability was evident in HCC cells but not in normal hepatocytes. Invasion was observed in gelatin-coated but not fibronectin-coated or type I collagen-coated membranes. Radiation upregulated matrix metalloproteinase-9 (MMP-9) mRNA level, MMP-9 protein level and MMP-9 activity. MMP-9 antisense oligonucleotides inhibited radiation-induced MMP-9 expression and thereby significantly inhibited radiation-induced HCC invasion. Furthermore, phosphatidylinositol 3-kinase (PI3K)/Akt chemical inhibitors LY294002 and wortmannin suppressed radiation-induced MMP-9 mRNA expression. Transient transfection with dominant-negative Akt plasmid also showed that the PI3K/Akt-signaling pathway was involved in this radiation-induced MMP-9 expression. Moreover, nuclear factor-kappaB (NF-kappaB) decoy oligodeoxynucleotide suppressed radiation enhanced MMP-9 promoter activity completely. PI3K/Akt chemical inhibitors inhibited radiation-induced NF-kappaB-driven luciferase promoter activity. Taken together, our results indicated that sublethal dose of radiation could enhance HCC cell invasiveness by MMP-9 expression through the PI3K/Akt/NF-kappaB signal transduction pathway.

Positive and Negative Affects in Living Kidney Donors.

OBJECTIVE: This study aimed to identify the factors influencing the positive and negative affects and the health-related quality of life (HRQOL) of living kidney donors. METHODS: With the use of a cross-sectional study design and a structured questionnaire, information on the basic characteristics, positive affect, negative affect, and HRQOL of 41 living kidney donors were compared. RESULTS: The negative affect in living kidney donors was similar to that of the general population, but the positive affect was slightly lower. The physical HRQOL of living kidney donors was slightly higher than that of the general population, and the mental HRQOL was similar. Female donors showed a greater positive affect than male donors. The donors who were siblings of the recipients showed a more negative affect. Donors without chronic disease and with good perceived physical health showed improved positive affect, negative affect, and mental HRQOL. Furthermore, living kidney donors with better positive and negative affects showed improved physical and mental HRQOLs. CONCLUSIONS: Clinical health providers should evaluate and determine the positive affect, negative affect, and quality of life of living kidney donors, especially in men, siblings of the recipients, those with chronic disease, and those with poorer perceived physical health. Moreover, psychosocial interventions should be provided to improve these factors.

Atomic Configuration of Point Defect Clusters in Ion-Irradiated Silicon Carbide.

Silicon Carbide (SiC) is a promising cladding material for accident-tolerant fuel in light water reactors due to its excellent resistance to chemical attacks at high temperatures, which can prevent severe accident-induced environmental disasters. Although it has been known for decades that radiation-induced swelling at low temperatures is driven by the formation of black spot defects with sizes smaller than 2 nm in irradiated SiC, the structure of these defect clusters and the mechanism of lattice expansion have not been clarified and remain as one of the most important scientific issues in nuclear materials research. Here we report the atomic configuration of defect clusters using Cs-corrected transmission electron microscopy and molecular dynamics to determine the mechanism of these defects to radiation swelling. This study also provides compelling evidence that irradiation-induced point defect clusters are vacancy-rich clusters and lattice expansion results from the homogenous distribution of unrecovered interstitials in the material.

Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity.

Alphavirus vectors have emerged as a promising strategy for the development of cancer vaccines and gene therapy applications. In this study, we used the replication-defective vaccine vector SIN replicon particles from a new packaging cell line (PCL) to develop SIN replicon particles encoding calreticulin (CRT) linked to a model tumor antigen, human papillomavirus type 16 (HPV16) E7 protein. The linkage of CRT to E7 in SIN replicon particles resulted in a significant increase in E7-specific CD8(+) T-cell precursors and a strong antitumor effect against E7-expressing tumors in vaccinated mice. SINrep5-CRT/E7 replicon particles enhanced presentation of E7 through the major histocompatibility complex (MHC) class I pathway by infecting dendritic cells (DCs) directly and pulsing DCs with lysates of cells infected by SINrep5-CRT/E7 replicons. Vaccination of immunocompromised (BALB/c nu/nu) mice with SINrep5-CRT/E7 replicon particles also generated significant reduction of lung tumor nodules, suggesting that antiangiogenesis may contribute to the antitumor effect of SINrep5-CRT/E7 replicon particles. Furthermore, SINrep5-CRT/E7 replicon particles generated long-term in vivo tumor protection effects and antigen-specific memory immunities. We concluded that the CRT strategy used in the context of SIN replicon particles facilitated the generation of a highly effective vaccine for cancer prophylaxis and immunotherapy.

Factors influencing organotin distribution in different marine environmental compartments, and their potential health risk.

Tributyltin (TBT) and triphenyltin (TPT) in different marine environmental compartments such as seawater, sediments, and inshore fishes were investigated in 21 Taiwanese harbors between 2001 and 2004 in order to determine the major factors influencing their distribution. The existence of major input sources and the limited water exchange rate inside the harbors were indicated by higher TBT concentrations in seawater from inner harbor than from outer harbor areas. The levels of TBT in sediments were found to be mainly affected by their geographic distribution, water exchange rates and shipping activity. No significant correlations in TBT concentrations between water, sediment and fish suggested TBT accumulation by fish might not result from water and sediment, but from their food. TPT were detected in most fish samples, but found in few sediment samples and none in seawater, indicating fish could be as a target element for monitoring contaminated levels of TPT in the aquatic environment. Mean concentrations of TBT in fish muscle higher than tolerable average residue levels (TARLs), and mean hazard indices of TBT and TPT higher than 1 suggested consumption of fishes from Taiwanese harbor areas might have potential high risk to human health.

Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo.

Genistein, found in soy products, is a phytochemical with several biological activities. In the current study, our research focused on the estrogenic and proliferation-inducing activity of genistein. We have demonstrated that genistein enhanced the proliferation of estrogen-dependent human breast cancer (MCF-7) cells in vitro at concentrations as low as 10 nM, with a concentration of 100 nM achieving proliferative effects similar to those of 1 nM estradiol. Expression of the estrogen-responsive gene pS2 was also induced in MCF-7 cells in response to treatment with a concentration of genistein as low as 1 microM. At higher concentrations (above 20 microM), genistein inhibits MCF-7 cell growth. In vivo, we have shown that dietary treatment with genistein (750 ppm) for 5 days enhanced mammary gland growth in 28-day-old ovariectomized athymic mice, indicating that genistein acts as an estrogen in normal mammary tissue. To evaluate whether the estrogenic effects observed in vitro with MCF-7 cells could be reproduced in vivo, MCF-7 cells were implanted s.c. in ovariectomized athymic mice, and the growth of the estrogen-dependent tumors was measured weekly. Negative control animals received the American Institute of Nutrition (AIN)-93G diet, the positive control group received a new s.c. estradiol (2 mg) pellet plus the AIN-93G diet, and the third group received genistein at 750 ppm in the AIN-93G diet. Tumors were larger in the genistein (750 ppm)-treated group than they were in the negative control group, demonstrating that dietary genistein was able to enhance the growth of MCF-7 cell tumors in vivo. Increased uterine weights were also observed in the genistein-treated groups. In summary, genistein can act as an estrogen agonist in vivo and in vitro, resulting in the proliferation of cultured human breast cancer cells (MCF-7) and the induction of pS2 gene expression. Here we present new information that dietary genistein stimulates mammary gland growth and enhances the growth of MCF-7 cell tumors in ovariectomized athymic mice.

Factors Determining Physical and Mental Quality of Life of Living Kidney Donors in Taiwan.

BACKGROUND: Living-donor kidney transplantation has a positive influence on recipients' life expectancy and improves quality of life for patients with end-stage renal disease compared with dialysis patients. Evaluation of the physical and mental quality of life for donors can promote positive perceptions about donation and help potential donors in their decision-making process. The aim of this study was to explore the predictive factors of quality of life for living kidney donors. METHODS: A cross-sectional and descriptive design was used, and the study was conducted from January to July 2013. The donors were a convenience sample of 34 participants who had undergone kidney transplant surgery >1 year earlier. RESULTS: The results showed that kidney donors had a low to moderate physical and mental quality of life. Multiple regression analysis revealed that financial concerns and anxiety explained 27.8% of the total variance of quality of life in the physical component. Anxiety and paid work explained 61.4% of the total variance of quality of life in the mental component. CONCLUSIONS: After renal transplantation, living kidney donors experienced low to moderate quality of life. Because donors are family members (siblings, sons or daughters, spouses, or parents), monthly family income is a significant issue that influences both the decision to donate and quality of life after transplantation. Our findings suggest that pre-transplantation assessment must include social workers as part of the health care team to evaluate the impact of a donor's financial status on post-transplantation quality of life.