Seasonal changes in the circadian activity rhythm of light-dark (LD) and completely dark (DD) regimen in the mouse submandibular gland in the presence of light-dark (LD) and completely dark (DD) regimen

Influence of seasons on circadian activity changes and the influence of one and six weeks of DD upon these changes of acid phosphatase (AP) and beta-acetylglucosaminidase (AM) was studied in the submandibular gland of sexually mature male mice. Total enzyme activity was determined in tissue homogenates at four-hour intervals in March, June, October, and February under standard LD12/12 conditions and after one and six weeks of the DD regime. The rhythms were analysed according to cosinor method. Under constant lighting conditions the seasonal differences in the AM circadian activity rhythm were found. AP activity was considerably less influenced by seasonal changes. Both enzyme activity changes were independent of each other and each rhythm was differently influenced by DD. In the case of AM the most pronounced circadian activity changes had the highest amplitude and mesor occurred in summer. The strongest influence of DD upon this enzyme activity rhythm was observed in spring and summer especially after the first week, after six weeks the acrophase returned to the LD group value (spring). In autumn and winter the reaction to DD was different to that of summer and spring. For AP the circadian changes of activity were non-rhythmic in spring, whereas in all other seasons the acrophases occurred almost at the same time in the afternoon. In DD the activity rhythm significantly changed after six weeks. In all seasons, except spring the circadian rhythm of activity was not observed after six weeks of DD. An attempt was made to explain the observed results by the certain kind of genetic memory present in laboratory animals the neurohormonal system of which is influenced by seasonal changes.     

The survival and development of the shrimp Crangon crangon (L.), reared in the laboratory under non-circadian light-dark cycles

The shrimp, Crangon crangon (L.), has been reared from hatching to the late juvenile phase, under a circadian (LD 12 : 12) and two non-circadian (LD 8 : 8 and LD random) light-dark cycles. During the zoeal phase, survival in the non-circadian regimes was markedly lower than in the control circadian treatments. This effect supports the hypothesis that the entraining influence of daily environmental cycles is important in coordinating the various physiological processes within the animal. There was no evidence, however, that growth and morphological development were affected in the non-circadian regimes.     

The Notch pathway in prostate development and cancer

Abstract The Notch family of transmembrane receptors are important mediators of cell fate determination. Accordingly, Notch signaling is intimately involved in the development of numerous tissues. Recent findings have highlighted a critical role for Notch signaling in normal prostate development. Notch signaling is required for embryonic and postnatal prostatic growth and development, for proper cell lineage specification within the prostate, as well as for adult prostate maintenance and regeneration following castration and hormone replacement. Evidence for Notch as a regulator of prostate cancer development, progression, and metastasis has also emerged. This review summarizes our current understanding of the role of Notch pathway elements, including members of the Jagged, Delta-like, hairy/enhancer-of-split, and hairy/enhancer-of-split related with YRPW motif families, in prostate development and tumorigenesis. Data supporting Notch pathway elements as oncogenes and tumor suppressors in prostate tumors, as well as data implicating Notch receptors and ligands as potential markers of normal prostate stem/progenitor cells and prostate cancer stem/initiating cells, are also presented.     

Evaluation of a proposed breast cancer screening regimen.

The Forrest working group on breast cancer screening recommended routine mammography for women in the United Kingdom at ages 50, 53, 56, 59, 62, and 65. Benefits were costed at about 3000 pounds for each life year recovered, but there was no estimate of the cost of each life saved, and the consequent reduction in mortality from breast cancer in the general population of the United Kingdom was not estimated. The present study addressed both of these issues using an interactive computer modelling process. Long term savings were calculated at 900 deaths a year in England and Wales--that is, about 8% of the total deaths from breast cancer--and 9% of life years currently lost. The cost of each death saved from breast cancer was estimated at 39,000 pounds.     

Prevention of prostate cancer through custom tailoring of chemopreventive regimen

One practical way to control cancer is through chemoprevention, which refers to the administration of synthetic or naturally occurring agents to block, reverse or delay the process of carcinogenesis. For a variety of reasons, the most important of which is human acceptance, for chemopreventive intervention naturally occurring diet-based agents are preferred over synthetic agents. For a long time, the prevailing mantra of cancer chemoprevention has been: "Find effective agents with acceptable or no toxicity and use them in preventing cancer in relatively healthy people or individuals at high risk for developing cancer". In pursuing this goal many naturally occurring phytochemicals capable of affording protection against carcinogenesis in preclinical settings in experimental animals have been described. However, clinical trials of single agents have yielded disappointing results. Since carcinogenesis is a multistage phenomenon in which many normal cellular pathways become aberrant, it is unlikely that one agent could prove effective in preventing cancer. This review underscores the need to build an armamentarium of naturally occurring chemopreventive substances that could prevent or slow down the development and progression of prostate cancer. Thus, the new effective approach for cancer prevention "building a customized mechanism-based chemoprevention cocktail of naturally occurring substances" is advocated.     

Effect of an exercise regimen on development of hypertension in rats

The possibility that a forced exercise regimen might prevent the development of hypertension induced in rats both by renal encapsulation and chronic administration of deoxycorticosterone acetate (DOCA) and NaCl has been studied. In renal hypertensive rats, forced exercise at 0.4 to 1.25 miles/day, 7 days/wk for 16-22 wk failed to prevent the development of hypertension and cardiomegaly and reduced renal concentrating ability accompanying the hypertension. In DOCA-treated rats (10 mg/wk), forced exercise at 0.4 and 0.8 mile/day, 7 days/wk for 16 wk also failed to prevent both the development of hypertension and cardiomegaly. A review of data of others reveals that exercise may delay the development of hypertension in both Dahl salt-sensitive and spontaneously hypertensive (SHR) rats and may modestly reduce the maximal level of pressure attained. Of the four models of hypertension studied to date in rats, the Dahl salt-sensitive strain appears to be the one that responded best to exercise, although blood pressure eventually reached that of sedentary controls.     

The role of chemical and physical factors in cancer development

The author deals with the effects of environmental chemical-, and physical carcinogens playing predominant role in nearly 90% of the cancer development. Different steps of chemical carcinogenesis, classification and evaluation of carcinogens according to the criteria of International Agency for Research on Cancer, and the most important biological markers of genotoxic exposures are presented. Among physical agents the carcinogenic effects of ionizing and nonionizing radiations are demonstrated, including limited, inadequate or proved carcinogenic action of UV, microwave, static and low-frequency electric and magnetic fields.     

The interplay between innate and adaptive immunity regulates cancer development

There is increasing clinical and experimental evidence that inflammation and cancer are causally linked. Much progress has been made in understanding how inflammatory cells contribute to cancer development; however, it is still largely unknown which molecular mechanisms are responsible for initiation and maintenance of chronic inflammation associated with developing neoplasms. This review will discuss how the adaptive and innate immune systems interact during physiological and chronic inflammation, with a focus on studies revealing new insights into the role of adaptive immune cells as important regulators of chronic inflammation-associated carcinogenesis. We will speculate on whether current knowledge about the dysregulated interplay between adaptive and innate immunity during chronic inflammatory disorders might be useful in understanding and targeting the underlying mechanisms of chronic inflammation-associated neoplastic progression.This article is a symposium paper from the conference Tumor Escape and its Determinants, held in Salzburg, Austria, on 10–13 October 2004     

Cadherins in development and cancer

Proper embryonic development is guaranteed under conditions of regulated cell-cell and cell-matrix adhesion. The cells of an embryo have to be able to distinguish their neighbours as being alike or different. Cadherins, single-pass transmembrane, Ca(2+)-dependent adhesion molecules that mainly interact in a homophilic manner, are major contributors to cell-cell adhesion. Cadherins play pivotal roles in important morphogenetic and differentiation processes during development, and in maintaining tissue integrity and homeostasis. Changes in cadherin expression throughout development enable differentiation and the formation of various organs. In addition to these functions, cadherins have strong implications in tumourigenesis, since frequently tumour cells show deregulated cadherin expression and inappropriate switching among family members. In this review, I focus on E- and N-cadherin, giving an overview of their structure, cellular function, importance during development, role in cancer, and of the complexity of Ecadherin gene regulation.     

Integrins in development and cancer

The correct control of cell fate decisions is critical for metazoan development and tissue homeostasis. It is established that the integrin family of cell surface receptors regulate cell fate by mediating cell–cell and cell–extracellular matrix (ECM) interactions. However, our understanding of how the different family members control discrete aspects of cell biology, and how this varies between tissues and is temporally regulated, is still in its infancy. An emerging area of investigation aims to understand how integrins translate changes in tension in the surrounding microenvironment into biological responses. This is particularly pertinent due to changes in the mechanical properties of the ECM having been linked to diseases, such as cancer. In this review, we provide an overview of the roles integrins play in important developmental processes, such as proliferation, polarity, apoptosis, differentiation and maintenance of “stemness”. We also discuss recent advances in integrin mechanobiology and highlight the involvement of integrins and aberrant ECM in cancer.