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.
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.
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