Circadian rhythms regulate diverse physiologic processes, including homeostatic functions of steroid hormones and their receptors. Perturbations of these rhythms are associated with pathogenic conditions, such as depression, diabetes, and cancer. Androgens play an important role in both normal development and carcinogenesis of the prostate. In the present study, we investigated a potential role for the core clock factor Per1 in the pathogenesis of prostate cancer. Serum-shocked synchronized prostate cancer cells displayed disrupted circadian rhythms compared with the normal prostate tissue. Using Oncomine to perform a meta-analysis of microarray expression studies, we found that Per1 is downregulated in human prostate cancer samples compared with normal prostates. Reporter assays showed that Per1 inhibited transactivation of the androgen receptor (AR) both in 293T cells overexpressing the AR and in the prostate cancer cell line LNCaP. Forced expression of Per1 in LNCaP cells diminished the expression of known androgen-sensitive genes following stimulation with dihydrotestosterone. We showed that Per1 physically interacted with AR; in addition, we found that Per1 itself is regulated by androgens in prostate cancer cells. Overexpression of Per1 in prostate cancer cells resulted in significant growth inhibition and apoptosis. Our results support the emerging role of circadian genes as key players in malignant transformation. Further elucidating the connections between clock genes and the AR pathway could benefit the development of new therapeutic strategies for prostate cancer as well as provide insights into chronotherapy as a way to optimize current therapies.

No abstract

A 57-year old female was referred to our hospital because of flu like symptoms, and extensive bilateral pleural and pericardial effusion. However, the patient showed neither lymphadenopathy nor hepatosplenomegaly. Examination of cells in her pleural effusion revealed atypical cells with convoluted nuclear contour, dense chromatin, and bizarre mitotic figures. Numerous atypical cells had "flower shape" nuclei ( Figure 1A).. She was negative for HTLV-I virus. Similar abnormal cells were also detected in the peripheral blood and bone marrow.

Lung cancer is the most common cancer worldwide and is the leading cause of cancer death for both men and women in the USA. Symptom burden in patients with advanced lung cancer is very high and has a negative impact on their quality of life (QOL). Palliative care with its focus on the management of symptoms and addressing physical, psychosocial, spiritual, and existential suffering, as well as medically appropriate goal setting and open communication with patients and families, significantly adds to the quality of care received by advanced lung cancer patients. The Provisional Clinical Opinion (PCO) of American Society of Clinical Oncology (ASCO) as well as the National Cancer Care Network's (NCCN) clinical practice guidelines recommends early integration of palliative care into routine cancer care. In this chapter, we will provide an overview of palliative care in lung cancer and will examine the evidence and recommendations with regard to a comprehensive and interdisciplinary approach to symptom management, as well as discussions of goals of care, advance care planning, and care preferences.

228 Background: ECOG-PS is a widely implemented scale in oncology to assess performance status (PS). Higher scores are associated with poorer tolerance to higher-intensity chemotherapy (Ct). While professional societies recommend limiting Ct in patients with solid tumors and poor PS, the practice remains pervasive. To reduce this practice, in 2014 the Cedars-Sinai (CS) cancer quality committee developed a quality initiative (QI) requiring oncologists to indicate ECOG-PS on IV chemotherapy orders, with a structured hard-stop to evaluate patients with ECOG-PS≥3. Previously ECOG-PS was not required. Ct nurses also scored ECOG-PS, though their evaluation was not reported back to oncologists, and did not affect Ct decisions. Earlier studies have suggested a bias for oncologists to rate the ECOG-PS more positively than nurses when evaluating the same patient. Methods: 1084 of the total 12,259 Ct orders activated from 3/1/14-2/28/15 in a CS infusion center were randomly audited for ECOG-PS scoring by MD and RN for quality assurance. Completion and concordance rates for ECOG-PS were determined. Results: 93% and 83% of charts documented MD and RN ECOG-PS, respectively. 827 charts had both MD and RN ECOG-PS scores. Concordance rates, and discordance directionality are described in the Table. Conclusions: This QI achieved high rates of ECOG-PS documentation by oncologists, and low rates of Ct administration to patients with ECOG-PS≥3. MD/RN concordance rates were similar to those described in the literature. Interestingly, and in stark contrast to previous studies, MDs were more likely to score ECOG-PS as poorer compared to RNs in solid tumor discordant cases. [Table: see text]

Individuals who are on long-term opioid therapy (LTOT) for chronic noncancer pain are frequently admitted to the hospital with acute pain, exacerbations of chronic pain, or comorbidities. Consequently, hospitalists find themselves faced with complex treatment decisions in the context of uncertainty about the effectiveness of LTOT as well as concerns about risks of overdose, opioid use disorders, and adverse events. Our multidisciplinary team sought to synthesize guideline recommendations and primary literature relevant to assessing medical inpatients on LTOT, with the objective of assisting practitioners in balancing effective pain treatment and opioid risk reduction. We identified no primary studies or guidelines specific to assessing medical inpatients on LTOT. Recommendations from outpatient guidelines on LTOT and guidelines on pain management in acute-care settings include the following: evaluate both pain and functional status, differentiate acute from chronic pain, investigate the preadmission course of opioid therapy, obtain a psychosocial history, screen for mental health conditions, screen for substance use disorders, check state prescription drug monitoring databases, order urine drug immunoassays, detect use of sedative-hypnotics, and identify medical conditions associated with increased risk of overdose and adverse events. Although approaches to assessing medical inpatients on LTOT can be extrapolated from related guidelines, observational studies, and small studies in surgical populations, more work is needed to address these critical topics for inpatients on LTOT.

<div>Abstract<p>Circadian rhythms regulate diverse physiologic processes, including homeostatic functions of steroid hormones and their receptors. Perturbations of these rhythms are associated with pathogenic conditions, such as depression, diabetes, and cancer. Androgens play an important role in both normal development and carcinogenesis of the prostate. In the present study, we investigated a potential role for the core clock factor Per1 in the pathogenesis of prostate cancer. Serum-shocked synchronized prostate cancer cells displayed disrupted circadian rhythms compared with the normal prostate tissue. Using Oncomine to perform a meta-analysis of microarray expression studies, we found that <i>Per1</i> is down-regulated in human prostate cancer samples compared with normal prostates. Reporter assays showed that Per1 inhibited transactivation of the androgen receptor (AR) both in 293T cells overexpressing the AR and in the prostate cancer cell line LNCaP. Forced expression of <i>Per1</i> in LNCaP cells diminished the expression of known androgen-sensitive genes following stimulation with dihydrotestosterone. We showed that Per1 physically interacted with AR; in addition, we found that Per1 itself is regulated by androgens in prostate cancer cells. Overexpression of <i>Per1</i> in prostate cancer cells resulted in significant growth inhibition and apoptosis. Our results support the emerging role of circadian genes as key players in malignant transformation. Further elucidating the connections between clock genes and the AR pathway could benefit the development of new therapeutic strategies for prostate cancer as well as provide insights into chronotherapy as a way to optimize current therapies. [Cancer Res 2009;69(19):7619–25]</p></div>

Supplementary Table 2 from A Role for the Clock Gene <i>Per1</i> in Prostate Cancer