Association between dysphagia risk and unplanned hospitalization in older patients receiving home medical care.

AIM: Home medical care for older adults with chronic conditions is becoming an increasing important issue in Japan. We need to support long-term medical care at home and avoid unplanned hospitalizations, which can adversely affect activities of daily living and quality of life. In this study, we investigated whether swallowing function is a risk for unplanned hospitalization in older patients with functional decline who are receiving home medical care. METHODS: In the current study, we examined data obtained in the Observational study of Nagoya Elderly with HOme MEdical study (ONEHOME) that investigated the medical health of older adults receiving home medical care services in Nagoya City, Japan. The data analyzed were patients' age, sex, number of medications, Dysphagia Severity Scale, Charlson Comorbidity Index, Barthel Index, Mini Nutritional Assessment - Short Form, Frailty Index and dementia independent scale. The Dysphagia Severity Scale was categorized into the presence or absence of dysphagia risk. The association between dysphagia risk and days until first hospitalization was investigated by Cox regression analysis. RESULTS: In total, 86 out of 178 patients had a hospitalization during the study period of 4 years. Cox regression analysis with adjustment for age, sex, Charlson Comorbidity Index, Barthel Index and Mini Nutritional Assessment - Short Form scores showed that a lower Dysphagia Severity Scale score was significantly associated with unexpected hospitalization. CONCLUSIONS: Dysphagia risk predicts the first unexpected hospitalization in older individuals receiving home medical care. Patients' swallowing function is an important factor for estimating prognosis. Geriatr Gerontol Int 2019; 19: 977-981.

Potentially inappropriate medications according to STOPP-J criteria and risks of hospitalization and mortality in elderly patients receiving home-based medical services.

BACKGROUND: Although potentially inappropriate medications (PIMs) have been linked to poor health outcomes, country-specific PIM criteria have not been compared. Thus, we compared the identification of PIMs between the Screening Tool for Older Person's Appropriate Prescriptions for Japanese (STOPP-J) and the 2015 American Geriatrics Society Beers Criteria in elderly patients receiving home-based medical services. METHODS: A 5-year prospective cohort study was conducted with 196 patients receiving home-based medical services. Data were collected using questionnaires and chart reviews and included detailed information on prescription medication. STOPP-J and the Beers Criteria were used to categorize PIM and non-PIM recipients. All-cause mortality and first hospitalization were compared using a multivariate Cox regression model. RESULTS: PIMs were detected in 132 patients (67.3%) by STOPP-J and in 141 patients (71.9%) by the Beers Criteria, and the mean numbers of PIMs were 1.3 ± 1.3 and 1.2 ± 1.1, respectively. The three most frequently prescribed STOPP-J PIMs were hypnotics (26.8%), diuretics (25.6%), and NSAIDs (12.6%), compared with proton pump inhibitors (PPIs) (29.8%), hypnotics (26%), and NSAIDs (8.1%) according to the Beers Criteria. STOPP-J PIMs were associated with all-cause mortality (HR 3.01, 95% CI 1.37-6.64) and hospitalization (HR 1.91, 95% CI 1.17-3.09); neither was associated with Beers Criteria PIMs. Using a modified Beers Criteria (excluding PPIs), PIMs were correlated with first hospitalization (HR 1.91, 95% CI 1.17-3.09). CONCLUSIONS: PIMs categorized by STOPP-J are associated with hospitalization and mortality in Japanese patients receiving home-based medical services. PPIs, commonly used for acid-related diseases, do not seem to have deleterious effects on health outcomes. Country-oriented, medication-specific criteria would be of considerable clinical utility.

Change in quality of life and potentially associated factors in patients receiving home-based primary care: a prospective cohort study.

BACKGROUND: The trajectories for health-related quality of life of patients receiving home-based primary care are not well identified. Our objective was to investigate changes in the quality of life (QOL) and factors that affected the QOL of patients receiving home-based primary care. METHODS: Our prospective cohort study, the Observational study of Nagoya Elderly with HOme MEdical (ONE HOME) study, recruited 184 patients undergoing home-based primary care with a 5-year follow-up period. Patients' demographic data, socioeconomic status, physical diseases, medication use, feeding intake status, nutritional status, and functional status were measured annually. The 4-item quality of life index (QOL-HC [home care]) including self-perceived and family-reported QOL ratings that had been developed and previously validated in home care settings was used. Linear regression models were used for cross-sectional and longitudinal analyses. RESULTS: The participants' mean age was 78.8 ± 10.8 years, and 55.9% of the sample was male. Most patients were frail, disabled, and/or malnourished. Self-perceived and family-reported QOL scores dropped sequentially on annual follow-ups. In the multivariate longitudinal analysis, patients who were divorced (ß = 1.74) had high baseline QOL scores (ß = 0.75) and reported higher QOL ratings. In addition, high functional dependency was associated with a low self-perceived QOL rating, with a ß-value of - 1.24 in the pre-bedridden group and - 1.39 in the bedridden group. Given the family-reported QOL rating, the baseline QOL scores (ß = 0.50) and Mini-Nutritional Assessment-Short-Form scores (ß = 0.37) were found to have positive associations with the QOL rating. CONCLUSIONS: For the disabled receiving home-based primary care, independent functional status and divorce were positively associated with better self-perceived QOL, whereas nutritional status was correlated with better family-reported QOL.

Prevalence and risk factors of constipation and pollakisuria among older home-care patients.

AIM: The prevalence of constipation and prevalence of pollakisuria among older patients receiving home medical care have not been reported, and risk factors for these symptoms are not clear in this setting. The present study sought to determine the prevalence and risk factors of constipation and pollakisuria among older patients receiving home medical care in Japan. METHODS: This study utilized data from patients in the Observational Study of Nagoya Elderly with Home Medical Care (n = 153). We carried out univariate and multivariate logistic regression analyses with the presence of constipation or pollakisuria as the dependent variable to evaluate the relationships between constipation or pollakisuria and several covariates. RESULTS: The prevalence of constipation and pollakisuria were 56.9% and 15.7%, respectively. Multivariate logistic analysis showed that constipation was associated with Charlson Comorbidity Index score, polypharmacy and pollakisuria, and pollakisuria was associated with constipation and insomnia. Cardiovascular disease was inversely associated with constipation. CONCLUSIONS: The prevalence of constipation among home-care patients was as high as that reported for nursing home residents and higher than that among community-dwelling individuals. Clinicians should be aware of increased constipation risk among home-care patients, particularly for those with a high Carlson Comorbidity Index score, polypharmacy and/or pollakisuria. Geriatr Gerontol Int 2019; 19: 277-281.

[Agreement in the responses to self-reported and proxy-reported versions of QOL-HC: a new quality-of-life scale for patients receiving home-based medical care].

AIM: We developed quality-of-life (QOL) scales for patients receiving home medical care. The objective of this study was to examine the agreement between the scores of the scales answered by patients and those answered by their proxy, as cognitive decline may interfere with one's ability to understand complex topics, such as the QOL. METHODS: Participants were pairs of patients receiving home medical care and their proxy. The patients were asked to complete self-reported QOL scales (QOL-HC), and their proxies were asked to complete proxy-reported versions of the QOL scales (QOL-HC for caregivers). We then statistically examined the extent of agreement between the self- and proxy-reported QOL-HC scores using contingency tables and Spearman's rank correlation coefficient. The SPSS software program, version 24, was used for all statistical analyses. RESULTS: The concordance rate between patients and caregivers for questions 1 ( "Do you have peace of mind?" ), 2 ( "Do you feel satisfied with your life when you reflect on it?" ), 3 ( "Do you have someone that you spend time talking with?" ), and 4 ( "Are you satisfied with the home care service system?" ) were 52.3%, 52.3%, 79.5%, and 81.8%, respectively. The total scores for the patients and caregivers were significantly correlated (Spearman's ρ=0.364*). CONCLUSIONS: We created the first QOL scale for patients receiving home-based medical care and for caregivers. The findings of this study suggest that the QOL-HC can be used in clinical practice for the assessment of patients receiving professional home care.

Pathological significance and prognostic significance of FES expression in bladder cancer vary according to tumor grade.

PURPOSE: The feline sarcoma oncogene protein (FES) is a non-receptor tyrosine kinase implicated in both oncogenesis and tumor suppression. Here, cancer cell lines and human tissues were employed to clarify the pathological and prognostic significance of FES in bladder cancer. METHODS: The relationship between FES expression and cancer aggressiveness was investigated using 3 cell lines (T24: corresponding to grade 3, 5637: corresponding to grade 2, and RT4: corresponding to grade 1) and 203 tissues derived from human bladder malignancies. Proliferation, invasion, and migration of cancer cells were assessed following the knockdown (KD) of FES expression by the siRNA method. Relationships between FES expression and pathological features, aggressiveness, and outcome were investigated. RESULTS: FES-KD inhibited the proliferation, migration, and invasion of T24 cells but not of RT4 cells and 5637 cells. Considering all patients, FES expression demonstrated a negative relationship with grade but no association with muscle invasion or cancer cell proliferation. However, it was positively correlated with pT stage and cell proliferation in high-grade tumors (p = 0.002); no such association was found for low-grade tumors. In addition, elevated FES expression was a negative prognostic indicator of metastasis after radical surgery for patients with high-grade tumors (p = 0.021) but not for those with low-grade malignancies. CONCLUSIONS: FES appeared to act as a suppressor of carcinogenesis, being associated with low tumor grade in the overall patient group. However, its expression correlated with cancer aggressiveness and poor outcome in high-grade bladder cancer. FES, therefore, represents a potential therapeutic target and useful prognostic factor for such patients.

Factors associated with polypharmacy in elderly home-care patients.

AIM: Polypharmacy, which is often observed in elderly patients, has been associated with several unfavorable outcomes, including an increased risk of potentially inappropriate medications, medication non-adherence, drug duplication, drug-drug interactions, higher healthcare costs and adverse drug reactions. A significant association between polypharmacy and adverse outcomes among older people living in the community has also been confirmed. A reduction in the number of medications should thus be pursued for many older individuals. Nevertheless, the factors associated with polypharmacy in elderly home-care patients have not been reported. Here, we investigated those factors in elderly home-care patients in Japan. METHODS: We used the data of the participants in the Observational Study of Nagoya Elderly with Home Medical investigation. Polypharmacy was defined as the current use of six or more different medications. We carried out univariate and multivariate logistic regression analyses to assess the associations between polypharmacy and each of several factors. RESULTS: A total of 153 home-care patients were registered. The mean number of medications used per patient was 5.9, and 51.5% of the patients belonged to the polypharmacy group. The multivariate model showed that the patients' scores on the Charlson Comorbidity Index and the Mini-Nutrition Assessment Short Form were inversely associated with polypharmacy, and potentially inappropriate medication was most strongly associated with polypharmacy (odds ratio 4.992). CONCLUSIONS: The present findings showed that polypharmacy was quite common among the elderly home-care patients, and they suggest that home-care physicians should prescribe fewer medications in accord with the deterioration of home-care patients' general condition. Geriatr Gerontol Int 2018; 18: 33-41.

Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival.

Fps/Fes related (Fer) is a non-receptor tyrosine kinase that is expressed in fibroblasts, immune cells and endothelial cells. Fer serves an important pathological role in cell survival, angiogenesis and the immune system. However, the pathological role of Fer expression in the stromal cells surrounding renal cell carcinoma (RCC) has not been previously investigated. In the present study, immunohistochemical analysis of Fer was performed using the formalin-fixed tissue samples of 152 patients with RCC. The proliferative and apoptotic indices were used to represent the percentage of proliferation marker protein Ki-67- and cleaved caspase-3-positive cells, respectively. The microvessel density was defined as the number of cluster of differentiation (CD) 31-positively stained vessels/mm2. In addition, CD57+ and CD68+ cells were counted using semi-quantification of natural killer (NK) cells and macrophages. Fer expression in stromal cells was negatively associated with Fuhrman grade, pathological tumor stage and metastasis (P<0.001). Fer expression in stromal cells was negatively associated with CD68+ macrophage density, whereas it was positively associated with CD57+ NK cell density. Kaplan-Meier estimators indicated that decreased stromal Fer expression was a predictive marker of decreased cause-specific survival rate (P<0.001). Furthermore, low expression of Fer was identified as being an independent marker of decreased cause-specific survival using multivariate analysis (hazard ratio, 7.4; 95% confidence interval, 1.7-33.0; P<0.001). The results of the present study suggested that low Fer expression in stromal cells is associated with increased malignant aggressiveness and decreased survival in patients with RCC. CD57+ NK cell and CD68+ macrophage regulation in cancer-stromal tissue is considered to affect RCC pathology.

Factors associated with unexpected admissions and mortality among low-functioning older patients receiving home medical care.

AIM: The need for and availability of home medical care for elderly patients with limitations in terms of access to medical facilities has been increasing. We investigated the association between low function, malnutrition, dementia and multicomorbidity with patient prognosis, focusing on unexpected hospital admissions and mortality in elderly non-cancer patients receiving home care. METHODS: The study included 124 Japanese patients receiving home medical care in the form of regular visits from doctors and nurses for physical and/or mental disability. RESULTS: Of the patients studied, 36.2% experienced hospital admission. Student's t-test showed that admitted patients had significantly higher Charlson Comorbidity Index scores. Meanwhile, 19.6% of patients died during the course of the study. Student's t-test showed that older patients had a higher risk of mortality, and significantly lower activities of daily living and Mini-Nutritional Assessment Short-Form scores. Cox hazard analysis showed that multicomorbidity was a risk for unexpected hospital admission, and malnutrition was a risk for mortality in frail older adults receiving home medical care. CONCLUSIONS: We found that multicomorbidity was a risk for unexpected hospital admission, and malnutrition was a risk for mortality in frail older adults receiving home medical care. Geriatr Gerontol Int 2017; 17: 1623-1627.

Development and validation of a new quality of life scale for patients receiving home-based medical care: The Observational Study of Nagoya Elderly with Home Medical Care.

AIM: To develop and validate a scale that assesses quality of life in patients receiving home-based medical care. METHODS: A new quality of life scale was developed and evaluated in four phases: (i) item generation; (ii) first field study with a 14-item questionnaire; (iii) preliminary validation study, to reduce the number of items to four; and (iv) second field study comprising 40 patients, to evaluate the validity of the final version. Participants were requested to answer both the final version of the scale and the Short Form-8, to enable identification of any relationship between the two. RESULTS: Items were generated after discussions with doctors and care managers, and 14 items were selected for the draft version. In the preliminary validation study, 10 items were deleted, based on the results of statistical analysis of the data from the first field study. A psychometric analysis showed that the final four-item questionnaire had internal consistency (Cronbach's α = 0.7), and a significant association with the Short Form-8. CONCLUSIONS: We created the first quality of life scale for patients receiving home-based medical care. The scale's internal consistency was confirmed, as well as its external validity. This scale can be used independently of factors such as a patient's age, sex, level of independence in the presence of dementia or disability, swallowing function, hearing ability and communication ability, and can be used with ease in routine clinical practice. Geriatr Gerontol Int 2017; 17: 440-448.

Heme oxygenase-1 expression is associated with tumor aggressiveness and outcomes in patients with bladder cancer: a correlation with smoking intensity.

Heme oxygenase (HO)-1 is upregulated in malignancies and, in turn, regulates other cancer-related factors. Although HO-1 expression has been associated with cigarette smoking under various pathologic conditions, little is known about their association in patients with bladder cancer. HO-1 expression was assessed in 215 formalin-fixed bladder cancer specimens by immunohistochemistry. Microvessel density, lymph vessel density (LVD), proliferation index (PI), and expression of the vascular endothelial growth factor (VEGF)-A, -C, and -D, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, and MMP-9 were investigated by similar methods. Multivariate analyses were performed to evaluate the pathologic role and predictive value of HO-1 expression. Our results demonstrated that HO-1 expression was positively associated with T stage, lymph node metastasis, and grade. HO-1 expression was also positively correlated with PI, LVD, and expression levels of VEGF-D, COX-2, MMP-2, and MMP-9 (P < 0.001). In addition, multivariate analyses showed that HO-1 expression positively correlated with smoking intensity. Positive HO-1 expression was a significant predictor of subsequent metastasis (P = 0.008) and poor cause-specific survival (P < 0.001). Similarly, multivariate analyses showed that HO-1 expression was a predictor of cause-specific survival (hazard ratio = 3.13, P = 0.013). In conclusion, pathologic changes of HO-1-related factors were dependent on smoking intensity. Smoking upregulated HO-1 expression, and HO-1 was associated with malignant behavior of bladder cancer. Cancer cell proliferation, lymphangiogenesis, and expression levels of VEGF-D, COX-2, and MMP-2 played important roles in these HO-1-related effects. The clinical correlations of HO-1 were regulated by a complex mechanism that depended on smoking intensity.

High expression of Twist is associated with tumor aggressiveness and poor prognosis in patients with renal cell carcinoma.

AIMS: Twist has been reported to play crucial roles for malignant aggressiveness; however, detailed pathological significance of Twist in renal cell carcinoma (RCC) is not fully understood. The present study was to clarify clinical significance and molecular functions of Twist in patients with RCC. METHODS: Twist expression was examined by immunohistochemical techniques in 156 formalin-fixed specimens. Cell proliferation, angiogenesis, and apoptosis were measured as the percentage of Ki-67-positive cells (proliferation index, PI), CD31-stained vessels (microvessel density, MVD), and TUNEL-positive cells (apoptotic index, AI). In addition, semi-quantification of matrix metalloproteinase (MMP)-2 was performed. Macrophages were identified with anti-CD68 antibody, and the tumor associated macrophage (TAM) density was calculated as CD68-positive cells per high-power field. RESULTS: Twist expression was positively associated with grade, pT stage, and metastasis (p<0.001). We also noticed that its expression was considerably higher in cancer cells of sarcomatoid RCC and in those at the edge of the tumors. Twist expression was positively correlated with PI, MVD, MMP2 expression, and TAM density (P<0.001), but not with AI, and MMP-2 expression and TAM density were independently correlate by multi-variate analyses. Kaplan-Meir survival curves showed high Twist expression was a worse predictor for cause-specific survival (P<0.001). CONCLUSIONS: Twist plays important roles in tumor growth, progression, and survival in patients with RCC patients. Such pathological mechanisms are significantly associated with increased cancer cell proliferation, angiogenesis, MMP2 expression, and macrophage recruitment. These findings are important information for discussion of treatment and observation strategies in these patients.

Feline sarcoma-related protein expression correlates with malignant aggressiveness and poor prognosis in renal cell carcinoma.

Feline sarcoma-related protein (Fer) is a ubiquitously expressed non-receptor protein tyrosine kinase associated with proliferation in various cancer cells. However, no reports have described the pathological roles and prognostic value of Fer expression in renal cell carcinoma (RCC). We investigated Fer expression in three RCC cell lines (ACHN, Caki-1, and Caki-2) and in normal tubule cells (HK-2) by immunoblotting. Fer expression was highest in ACHN cells, with Caki-1 showing intermediate levels and Caki-2 showing low levels, and was undetectable in HK-2. RNA interference was therefore used to assess the effects of Fer knockdown in ACHN. Knockdown of Fer expression was found to inhibit RCC cell proliferation and colony formation. Immunohistochemical analysis of 131 human RCC tissues (110 conventional, 11 chromophobe, and 10 papillary) investigated relationships between Fer expression and clinicopathological features, including cancer cell proliferation, apoptosis, and prognostic value for survival. In human tissues, Fer expression was significantly higher in cancer cells than in normal tubules. In addition, expression levels correlated with cancer cell proliferation, but not with apoptosis. Multivariate analysis indicated associations of Fer expression with pT stage, tumor grade, and metastasis (P < 0.001). Fer expression was also prognostic for cause-specific survival according to multivariate analysis (hazard ratio, 3.89; 95% confidence interval, 1.02-14.84, P = 0.047). Fer expression correlates with RCC cell proliferation both in vitro and in vivo, and with tumor progression and survival. This represents useful information for discussing the pathological and clinical significance of Fer in RCC.

Small-molecule inhibitors of the c-Fes protein-tyrosine kinase.

The c-Fes protein-tyrosine kinase modulates cellular signaling pathways governing differentiation, the innate immune response, and vasculogenesis. Here, we report the identification of types I and II kinase inhibitors with potent activity against c-Fes both in vitro and in cell-based assays. One of the most potent inhibitors is the previously described anaplastic lymphoma kinase inhibitor TAE684. The crystal structure of TAE684 in complex with the c-Fes SH2-kinase domain showed excellent shape complementarity with the ATP-binding pocket and a key role for the gatekeeper methionine in the inhibitory mechanism. TAE684 and two pyrazolopyrimidines with nanomolar potency against c-Fes in vitro were used to establish a role for this kinase in osteoclastogenesis, illustrating the value of these inhibitors as tool compounds to probe the diverse biological functions associated with this unique kinase.

Pathological significance and predictive value for biochemical recurrence of c-Fes expression in prostate cancer.

BACKGROUND: c-Fes is a proto-oncogene encoded non-receptor protein-tyrosine kinase (PTK). However, genetic studies have indicated that it has anti-tumorigenic effects in certain cancers. The pathological and clinical significance of c-Fes in prostate cancer are unknown. METHODS: Expression of c-Fes was evaluated in normal glands, prostatic intraepithelial neoplasia (PIN), cancer cells in tissues of knock-in mouse adenocarcinoma prostate (KIMAP) model, and prostate cancer patients free of metastasis. Expression of c-Fes was analyzed by immunohistochemistry, and quantified by using the immunoreactivity score (IRS) (staining intensity × percentage of positive cells). Relationships between c-Fes expression and pT stage, Gleason's score (GS), and biochemical recurrence in patients who underwent radical surgery were also investigated. RESULTS: In KIMAP, the percentage in normal glands, PIN and cancer cells positive for c-Fes expression were 0 (0/7), 25.0 (2/8), and 100% (7/7), respectively. In human tissues, c-Fes expression was also significantly higher in cancer cells than in normal cells and PIN, and it correlated with pT stage (P < 0.001) and GS (P = 0.047). Multivariate analysis showed that c-Fes expression was an independent predictor of poor outcome poor prognosis (hazard ratio = 3.21, 95% confidence interval = 1.11-9.37, P = 0.032). CONCLUSION: The results suggested that c-Fes expression is a useful predictor of biochemical recurrence after radical surgery. The results also suggested that c-Fes is a potentially useful therapeutic target in prostate cancer and a predictor of biochemical recurrence after radical prostatectomy.

The contrasting oncogenic and tumor suppressor roles of FES.

The FES gene was first discovered as a protein-tyrosine kinase-encoding retroviral oncogene. The ability of v-FES to transform cells in vitro and initiate cancer in vivo has been established by cell culture, engraftment and transgenic mouse studies. The corresponding cellular c-FES proto-oncogene encodes a cytoplasmic FES protein-tyrosine kinase with restrained catalytic activity relative to its retrovirally encoded homologs. These observations have stimulated a search for mutations or inappropriate expression of c-FES in human cancers and research aimed at understanding the functions of the FES kinase and its potential involvement in cancer and other diseases. Paradoxically, although first identified as an oncogene, genetic evidence has also implicated c-fes as a potential tumor suppressor. This review will describe observations from basic and translational research which shapes our current understanding of the physiological, cellular and molecular functions of the FES protein-tyrosine kinase and its potential roles in tumorigenesis. We also propose a model to reconcile the conflicting oncogenic and tumor suppressor roles of c-FES in tumorigenesis.

Pathologic significance and prognostic value of phosphorylated cortactin expression in patients with sarcomatoid renal cell carcinoma.

OBJECTIVES: To clarify the clinical and prognostic significance of cortactin and phosphorylated cortactin in patients with sarcomatoid renal cell carcinoma (SRCC). METHODS: We retrospectively reviewed the data from 31 patients with SRCC and 33 with conventional renal cell carcinoma matched for clinicopathologic features. The immunoreactive score for cortactin, pY421 cortactin, and pY466 cortactin were measured using immunohistochemistry. The relationships between each immunoreactive score and the clinicopathologic features and survival were investigated. RESULTS: The immunoreactive score of p421 cortactin, but not that of cortactin and pY466 cortactin, was significantly greater in SRCC than in conventional renal cell carcinoma (P < .001). The expression of pY421 cortactin in SRCC correlated with the pT stage and metastasis (P < .001). The expression of pY466 cortactin showed a similar trend with pT stage (P = .043) but not with metastasis. Although both of pY421 cortactin and pY466 cortactin were identified as useful predictors for survival in univariate analyses, only pY421 cortactin expression was considered an independent predictor in patients with SRCC (odds ratio 4.53, 95% confidence interval 1.07-19.12, P = .040) in the multivariate analysis model, including pT stage and metastasis. CONCLUSIONS: Our results have demonstrated that phosphorylation of cortactin is a key process in malignant aggressiveness, and its expression is a useful predictor of cause-specific survival and could be a useful potential therapeutic target in patients with SRCC.

Clinical significance and predictive value of prostaglandin E2 receptors (EPR) 1 - 4 in patients with renal cell carcinoma.

BACKGROUND: The clinical significance of prostaglandin E2 receptor (EPR) expression in renal cell carcinoma (RCC) tissues remains unclear. Patients and Μethods: Four subtypes of EPRs were examined in 112 human RCC tissues by immunohistochemical and Western blot analysis. The relationships between EPR immunoreactivity score (IS) and various pathological features and survival were then analyzed. RESULTS: The IS of EP4R was significantly higher (p < 0.001) in cancer cells (mean = 2.7 and SD = 2.1) than in normal kidney tissues (1.8 and 1.2). EP4R expression correlated with pT stage, metastasis, and grade. EP2R expression was also associated with metastasis. Expressions of both EP2R and EP4R were found to be significant predictors for cause-specific survival on Kaplan-Meier survival analysis (p = 0.006 and 0.023, respectively). CONCLUSION: EP2R and EP4R may play important roles in malignant behavior. EP4R in particular was closely associated with pathological features, implicating this receptor as a potential therapeutic target in patients with RCC.

The c-Fes protein tyrosine kinase as a potential anti-angiogenic target in cancer.

Angiogenesis is implicated in many pathological conditions, including cancer progression. Novel approaches have enabled an understanding of how endothelial cellular processes are regulated in vivo during angiogenesis. Key players in angiogenesis are vascular endothelial growth factors (VEGFs) and Notch ligands. However, mechanisms of angiogenic responses by other proangiogenic factors in vivo are largely unknown. Research using cultured endothelial cells has shown that c-Fes is involved in the activation of phosphoinositide 3-kinase (PI3-kinase) downstream of a variety of cytokine receptors. The PI3-kinase/c-Akt pathway regulates cell survival, migration, and morphological differentiation of endothelial cells during angiogenesis, and c-Fes thus may be a potential target of anti-cancer therapy, especially for patients with anti-VEGF refractory cancer. In addition, a number of experiments have shown that a bone marrow-derived monocytic lineage regulates angiogenesis, and c-Fes is also expressed in these cells. Roles for c-Fes during angiogenesis will be the focus of extensive research in the future.

Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal therapy.

PURPOSE: X-linked inhibitor of apoptosis (XIAP) has high affinity and strong inhibitory activity on apoptosis-related caspase-3. The relationships between expression of XIAP and cleaved caspase-3, and response to neo-adjuvant hormonal therapy (NHT) remain elusive. The aim was to investigate whether NHT influences with XIAP expression in prostate cancer patients. In addition, the relationship between XIAP expression and apoptosis in patients who did or did not receive NHT was also investigated. METHODS: Eighty-three patients who had undergone radical prostatectomy were examined retrospectively and divided into NHT group (n = 40) and non-NHT group (n = 43). Immunohistochemistry was used to analyze the expressions of XIAP and cleaved caspase-3. The apoptotic cells reconfirmed the number of terminal deoxynucleotidyl transferase-mediated nick and labeling (TUNEL)-positive cells. RESULTS: In the non-NHT group, the proportion of TUNEL-positive cells correlated with expression of cleaved caspase-3 (r = 0.592, P < 0.001), and the expression of XIAP correlated negatively with that of cleaved caspase-3 and TUNEL-positive cells (r = -0.464, P < 0.001 and r = 0.431, P = 0.002, respectively). The expression of cleaved caspase-3, but not that of XIAP, was higher in NHT group than non-NHT group (P = 0.017). In the NHT group, there was no significant correlation between XIAP expression and cleaved caspase-3 expression or the proportion of TUNEL-positive cells. CONCLUSIONS: NHT did not influence XIAP expression. We speculate that the inhibition of XIAP expression may reinforce the apoptotic effect of NHT and improve the prognosis in patients with prostate cancer.