The association of quality of life with potentially remediable disruptions of circadian sleep/activity rhythms in patients with advanced lung cancer.

Background: 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.

Methods: 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.

Validation of actigraphy to assess circadian organization and sleep quality in patients with advanced lung cancer.

Background: 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.

Sunspot dynamics are reflected in human physiology and pathophysiology.

Periodic episodes of increased sunspot activity (solar electromagnetic storms) occur with 10-11 and 5-6 year periodicities and may be associated with measurable biological events. We investigated whether this sunspot periodicity characterized the incidence of Pap smear-determined cervical epithelial histopathologies and human physiologic functions. From January 1983 through December 2003, monthly averages were obtained for solar flux and sunspot numbers; six infectious, premalignant and malignant changes in the cervical epithelium from 1,182,421 consecutive, serially independent, screening Pap smears (59°9″N, 4°29″E); and six human physiologic functions of a healthy man (oral temperature, pulse, systolic and diastolic blood pressure, respiration, and peak expiratory flow), which were measured ∼5 times daily during ∼34,500 self-measurement sessions (44°56″N, 93°8″W).

Circadian transcription profile of mouse breast cancer under light-dark and dark-dark conditions.

The circadian clock exists in virtually every cell and regulates key biological processes in cells and tissues. Even in cancer cells, DNA synthesis, cell division and tumor growth are gated by the circadian clock. This study examined the gene expression profiles of transplanted mouse breast tumor cells under normal light-dark (LD) as well as constant dark (DD) conditions.

Circadian clock manipulation for cancer prevention and control and the relief of cancer symptoms.

Life has evolved on this planet with regular daily spans of direct solar energy availability alternating with nocturnal spans of dark. Virtually every earth-borne life form has factored this circadian pattern into its biology to ensure the temporal coordination with its resonating environment, a task essential for its individual survival and that of its species. The first whole genome inspections of mutations in human colon and breast cancer have observed specific retained clock gene mutations.

The circadian clock gene Per1 suppresses cancer cell proliferation and tumor growth at specific times of day.

Cell cycle progression is tightly regulated. The expressions of cell cycle regulators, the products of which either promote or inhibit cell proliferation, oscillate during each cell cycle. Cellular proliferation and the expression of cell cycle regulators are also controlled by the circadian clock.

Imaging multidimensional therapeutically relevant circadian relationships.

Circadian clocks gate cellular proliferation and, thereby, therapeutically target availability within proliferative pathways. This temporal coordination occurs within both cancerous and noncancerous proliferating tissues. The timing within the circadian cycle of the administration of drugs targeting proliferative pathways necessarily impacts the amount of damage done to proliferating tissues and cancers.

Actigraphic assessment of daily sleep-activity pattern abnormalities reflects self-assessed depression and anxiety in outpatients with advanced non-small cell lung cancer.

Objectives: We measured subjectively evaluated depression and anxiety, and objectively measured daily sleep-activity patterns in inpatients and outpatients with advanced non-small cell lung cancer (NSCLC) and determined whether cancer-associated depression and anxiety are accompanied by characteristic circadian rhythm abnormalities.

Methods: Equal numbers of inpatients (n=42) and outpatients (n=42) with advanced NSCLC were studied. Baseline depression and anxiety, assessed by the Hospital Anxiety and Depression Scale (HADS), and actigraphy were recorded before chemotherapy initiation.

Down regulation of circadian clock gene Period 2 accelerates breast cancer growth by altering its daily growth rhythm.

Purpose Per2, a core circadian clock gene, has tumor suppressor properties and is mutated or down regulated in human breast cancers. We have manipulated the expression of this gene in vitro and in vivo to more fully understand how the Per2 clock gene product affects cancer growth. Methods We used siRNA and shRNA to down regulate Per2 expression in vitro and in vivo and measured cancer cell proliferation, tumor growth rate and several molecular pathways relevant to cancer growth and their circadian organizations.

Seasonal modulation of post-resection breast cancer metastasis.

Background: Human breast cancer incidence, histopathologic grade, invasiveness, and mortality risk vary significantly throughout each year. In order to better understand this seasonal cancer biology, we investigated the circannual pattern of post-resection breast cancer metastasis, under genetically and environmentally controlled conditions.

Methods: Over a span of 14 consecutive years, we conducted 22 similar experiments to investigate metastatic biology of breast cancer among 1,214 C3HeB/FeJ female mice.

Circadian clock coordinates cancer cell cycle progression, thymidylate synthase, and 5-fluorouracil therapeutic index.

Dysregulated cellular proliferation is a characteristic property of cancer. We show that, despite this fact, cancers maintain high amplitude, circadian rhythms in their growth, DNA synthesis, and mitosis. These patterns are accompanied by the daily traverse of BMAL-1 protein between the cytoplasm, where it is produced, and nucleus, where it influences timing of cancer cell proliferation.

Sun exposure, sexual behavior and uterine cervical human papilloma virus.

We have previously observed marked seasonal fluctuations in the frequency of cervical smears positive for human papilloma virus (HPV) in a series of smears obtained in Holland, with a peak in the summer months, especially August. Here, we tested two possible mechanisms that might underlie this summer peak: (1) enhanced transmission of HPV due to increased seasonal sexual activity, or (2) suppression of immunity due to summertime population exposure to solar ultraviolet (UV) radiation. Data derived from a continuous series of >900,000 independent cervical smears obtained from 1983 to 1998 were assessed for histopathologic epithelial changes pathognomonic of HPV.

Season, sun, sex, and cervical cancer.

Introduction: Sunlight's UV B component, a known cellular immunosupressant, carcinogen, and activator of viral infections, is generally seasonally available. Venereal human papillomavirus (HPV) transmission, at least in part, causes cervical cancer. We have previously inspected the monthly rates of venereal HPV infection and sunlight fluency in Southern Holland over 16 consecutive years.

Daily coordination of cancer growth and circadian clock gene expression.

Background: Circadian coordination in mammals is accomplished, in part, by coordinate, rhythmic expression of a series of circadian clock genes in the central clock within the suprachiasmatic nuclei (SCN) of the hypothalamus. These same genes are also rhythmically expressed each day within each peripheral tissue.

Methods: We measured tumor size, tumor cell cyclin E protein, tumor cell mitotic index, and circadian clock gene expression in liver and tumor cells at six equispaced times of day in individual mice of a 12-h light, 12-h dark schedule.