A biotinylated paclitaxel derivative with an extra-long chain (LC-LC-biotin) spacer arm was synthesized using an improved synthetic reaction sequence. The biotinylated paclitaxel analogue retained ...excellent microtubule stabilizing activity in vitro. Furthermore, it was shown that this analogue can simultaneously engage streptavidin and the binding site on microtubules, making it suitable for localization studies or for the attachment of paclitaxel to solid substrates via a streptavidin linkage.
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We have previously reported that higher patient satisfaction (PS) with service quality is associated with favorable survival outcomes in a variety of cancers. However, we argued that patients with ...greater satisfaction might be the ones with better self-rated health (SRH), a recognized predictor of cancer survival. We therefore investigated whether SRH can supersede patient satisfaction as a predictor of survival in prostate cancer.
Nine hundred seventeen prostate cancer treated at four Cancer Treatment Centers of America(®) hospitals between July 2011 and March 2013. PS was measured on a 7-point scale ranging from "completely dissatisfied" to "completely satisfied". SRH was measured on a 7-point scale ranging from "very poor" to "excellent". Both were dichotomized into two categories: top box response (7) versus all others (1-6). Patient survival was the primary end point. Cox regression was used to evaluate the association between PS and survival controlling for covariates.
The response rate for this study was 72%. Majority of patients (n = 517) had stage II disease. Seven hundred eighty-seven (85.8%) patients were "completely satisfied". Three hundred nineteen (34.8%) patients had "excellent" SRH. There was a weak but significant correlation between satisfaction and SRH (Kendall's tau b = 0.18; p < 0.001). On univariate analysis, "completely satisfied" patients had a significantly lower risk of mortality (HR = 0.46; 95% CI: 0.25-0.85; p = 0.01). Similarly, patients with "excellent" SRH had a significantly lower risk of mortality (HR = 0.25; 95% CI: 0.11-0.58; p = 0.001). On multivariate analysis, SRH was found to be a significant predictor of survival (HR = 0.31; 95% CI: 0.12-0.79; p = 0.01) while patient satisfaction was not (HR = 0.76; 95% CI: 0.40-1.5; p = 0.40).
SRH supersedes patient satisfaction with service quality as a predictor of survival in prostate cancer. SRH should be used as a control variable in analyses involving patient satisfaction as a predictor of clinical cancer outcomes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The effect of cultured autologous oral keratinocyte suspension in fibrin glue on the healing of surgically produced oral mucosal wounds was assessed in the rabbit model. Using the light ...microscope and a digital image analysis system, the epithelization parameters (marginal epithelization and percentage of wound re-epithelization) were measured in haematoxylin–eosin stained sections of the wound area and compared with those of wounds treated with fibrin glue alone and untreated ones. The epithelization was significantly higher in keratinocytes plus fibrin glue-treated wounds on postoperative days 3 and 7. No significant differences were observed on postoperative day 1, when the healing process had just begun, and on postoperative day 14, when re-epithelization was completed or nearly completed in all groups. The inflammatory infiltration of the wounded mucosa was weakest in keratinocyte-treated wounds and strongest in untreated wounds. In conclusion, suspension of cultured autologous oral keratinocytes in fibrin glue significantly accelerates oral wound healing in the rabbit model and could be beneficial in the treatment of oral wounds in patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cancer patients routinely develop symptoms consistent with profound circadian disruption, which causes circadian disruption diminished quality of life. This study was initiated to determine the ...relationship between the severity of potentially remediable cancer-associated circadian disruption and quality of life among patients with advanced lung cancer.
We concurrently investigated the relationship between the circadian rhythms of 84 advanced lung cancer patients and their quality of life outcomes as measured by the EORTC QLQ C30 and Ferrans and Powers QLI. The robustness and stability of activity/sleep circadian daily rhythms were measured by actigraphy. Fifty three of the patients in the study were starting their definitive therapy following diagnosis and thirty one patients were beginning second-line therapy. Among the patients who failed prior therapy, the median time between completing definitive therapy and baseline actigraphy was 4.3 months, (interquartile range 2.1 to 9.8 months).
We found that circadian disruption is universal and severe among these patients compared to non-cancer-bearing individuals. We found that each of these patient's EORTC QLQ C30 domain scores revealed a compromised capacity to perform the routine activities of daily life. The severity of several, but not all, EORTC QLQ C30 symptom items correlate strongly with the degree of individual circadian disruption. In addition, the scores of all four Ferrans/Powers QLI domains correlate strongly with the degree of circadian disruption. Although Ferrans/Powers QLI domain scores show that cancer and its treatment spared these patients' emotional and psychological health, the QLI Health/Function domain score revealed high levels of patients' dissatisfaction with their health which is much worse when circadian disruption is severe. Circadian disruption selectively affects specific Quality of Life domains, such as the Ferrans/Powers Health/Function domain, and not others, such as EORTC QLQ C30 Physical Domain.
These data suggest the testable possibility that behavioral, hormonal and/or light-based strategies to improve circadian organization may help patients suffering from advanced lung cancer to feel and function better.
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The p97 AAA (ATPase associated with diverse cellular activities), also called VCP (valosin-containing protein), is an important therapeutic target for cancer and neurodegenerative diseases. p97 forms ...a hexamer composed of two AAA domains (D1 and D2) that form two stacked rings and an N-terminal domain that binds numerous cofactor proteins. The interplay between the three domains in p97 is complex, and a deeper biochemical understanding is needed in order to design selective p97 inhibitors as therapeutic agents. It is clear that the D2 ATPase domain hydrolyzes ATP in vitro, but whether D1 contributes to ATPase activity is controversial. Here, we use Walker A and B mutants to demonstrate that D1 is capable of hydrolyzing ATP and show for the first time that nucleotide binding in the D2 domain increases the catalytic efficiency (kcat/Km) of D1 ATP hydrolysis 280-fold, by increasing kcat 7-fold and decreasing Km about 40-fold. We further show that an ND1 construct lacking D2 but including the linker between D1 and D2 is catalytically active, resolving a conflict in the literature. Applying enzymatic observations to small-molecule inhibitors, we show that four p97 inhibitors (DBeQ, ML240, ML241, and NMS-873) have differential responses to Walker A and B mutations, to disease-causing IBMPFD mutations, and to the presence of the N domain binding cofactor protein p47. These differential effects provide the first evidence that p97 cofactors and disease mutations can alter p97 inhibitor potency and suggest the possibility of developing context-dependent inhibitors of p97.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
There is little data on the prevalence of use of dietary supplements in cancer, especially in light of the growing evidence that some dietary supplements can have adverse interactions with ...conventional cancer treatment. The purpose of this study was to investigate the use of dietary supplements among adult cancer patients in a community hospital comprehensive cancer center.
A survey of 227 new adult cancer patients presenting for treatment for the first time at Cancer Treatment Centers of America at Midwestern Regional Medical Center, between November 2001 and October 2003. Patients completed the McCune Questionnaire, a validated instrument that captures information on the use of 56 dietary supplements in cancer, at admission to the hospital.
Of the 227 patients, 73% used some form of dietary supplements during the 30 day period before the survey was conducted. Dietary supplement use was significantly higher (p = 0.04) in patients with colorectal (80%) and breast (75%) cancer as compared to patients with lung cancer (53%). Patients with stage II (86%) and III (76%) disease at diagnosis were more likely (p = 0.02) to use dietary supplements as compared to those with stage I (71%) disease at diagnosis, while those with stage IV (61%) disease at diagnosis were least likely to use them. Of the 80 patients who had received chemotherapy within the last 30 days, 71% had also used dietary supplements in that timeframe and 25% had consumed one or more herbal therapies that are suspected to have adverse interactions with chemotherapy. Of the 57 patients combining chemotherapy with dietary supplements, 52.6% did not consult a healthcare professional.
In our study, twenty-five percent of patients receiving chemotherapy were concurrently using dietary supplements suspected to have adverse interactions with chemotherapy, usually relying on information sources other than healthcare professionals. Given the prevalence rates of these agents, healthcare providers should systematically inquire about them, and consider the potential for drug-dietary supplement interactions in treatment planning.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The aim of this paper is to summarise the knowledge about the anatomy, embryology and anthropology of the mandible and the mandibular foramen and also to highlight the most important clinical ...implications of the current studies regarding anaesthesia performed in the region of the mandible. An electronic journal search was undertaken to identify all the relevant studies published in English. The search included MEDLINE and EMBASE databases and years from 1950 to 2012. The subject search used a combination of controlled vocabulary and free text based on the search strategy for MEDLINE using key words: 'mandible', 'mandibular', 'foramen', 'anatomy', 'embryology', 'anthropology', and 'mental'. The reference lists of all the relevant studies and existing reviews were screened for additional relevant publications. Basing on relevant manuscripts, this short review about the anatomy, embryology and anthropology of the mandible and the mandibular foramen was written.
Many cancer patients report poor sleep quality, despite having adequate time and opportunity for sleep. Satisfying sleep is dependent on a healthy circadian time structure and the circadian patterns ...among cancer patients are quite abnormal. Wrist actigraphy has been validated with concurrent polysomnography as a reliable tool to objectively measure many standard sleep parameters, as well as daily activity. Actigraphic and subjective sleep data are in agreement when determining activity-sleep patterns and sleep quality/quantity, each of which are severely affected in cancer patients. We investigated the relationship between actigraphic measurement of circadian organization and self-reported subjective sleep quality among patients with advanced lung cancer.
This cross-sectional and case control study was conducted in 84 patients with advanced non-small cell lung cancer in a hospital setting for the patients at Midwestern Regional Medical Center (MRMC), Zion, IL, USA and home setting for the patients at WJB Dorn Veterans Affairs Medical Center (VAMC), Columbia, SC, USA. Prior to chemotherapy treatment, each patient's sleep-activity cycle was measured by actigraphy over a 4-7 day period and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire.
The mean age of our patients was 62 years. 65 patients were males while 19 were females. 31 patients had failed prior treatment while 52 were newly diagnosed. Actigraphy and PSQI scores showed significantly disturbed daily sleep-activity cycles and poorer sleep quality in lung cancer patients compared to healthy controls. Nearly all actigraphic parameters strongly correlated with PSQI self-reported sleep quality of inpatients and outpatients.
The correlation of daily activity/sleep time with PSQI-documented sleep indicates that actigraphy can be used as an objective tool and/or to complement subjective assessments of sleep quality in patients with advanced lung cancer. These results suggest that improvements to circadian function may also improve sleep quality.
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