Effectiveness of photodynamic therapy for mammary and extra-mammary Paget's disease: a state of the science review

<p>Abstract</p> <p>Background</p> <p>Paget's disease is a rare skin disorder occurring in the breast (mammary) or in the groin, genital, peri-anal and axillary regions (extra-mammary). Typical treatment involves surgical excision, which in the case of extra-mammary Paget's disease, can lead to significant morbidity. Photodynamic therapy (PDT) which uses a topical or intravenous photosensitizing agent that is activated by a light source to ablate abnormal tissue, offers a minimally invasive alternative. The purpose of this study was to assess the effectiveness of photodynamic therapy in the treatment of Paget's disease.</p> <p>Methods</p> <p>Following Cochrane guidelines, a comprehensive systematic review of all clinical studies and reports examining the use of PDT for mammary and extra-mammary Paget's disease was conducted. Study quality was assessed using the Oxford Levels of Evidence Scale.</p> <p>Results</p> <p>21 retrospective and 2 prospective non-comparative studies were identified and included in the review: 9 case reports with 1-2 patients and 14 case series with 1-16 patients. These reports totalled 99 patients with 133 extra-mammary Paget's lesions and 3 patients (with 3 lesions) with mammary Paget's disease. Follow-up periods were typically one year or less, with 77/133 extra-mammary lesions exhibiting complete response to PDT. One recurrent mammary skin lesion and two mammary lesions treated concomitantly with surgery also exhibited complete responses.</p> <p>Conclusions</p> <p>Evidence of the effectiveness of PDT for Paget's disease is promising, but limited. This may, in part, be explained by the rarity of the condition, making controlled comparative clinical trials challenging.</p

Identification and manipulation of tumor associated macrophages in human cancers

Evading immune destruction and tumor promoting inflammation are important hallmarks in the development of cancer. Macrophages are present in most human tumors and are often associated with bad prognosis. Tumor associated macrophages come in many functional flavors ranging from what is known as classically activated macrophages (M1) associated with acute inflammation and T-cell immunity to immune suppressive macrophages (M2) associated with the promotion of tumor growth. The role of these functionally different myeloid cells is extensively studied in mice tumor models but dissimilarities in markers and receptors make the direct translation to human cancer difficult. This review focuses on recent reports discriminating the type of infiltrating macrophages in human tumors and the environmental cues present that steer their differentiation. Finally, immunotherapeutic approaches to interfere in this process are discussed

Ontogeny of central serotonergic neurons in the directly developing frog, Eleutherodactylus coqui

Embryonic development of the central serotonergic neurons in the directly developing frog, Eleutherodactylus coqui , was determined by using immunocytochemistry. The majority of anuran amphibians (frogs) possess a larval stage (tadpole) that undergoes metamorphosis, a dramatic post-embryonic event, whereby the tadpole transforms into the adult phenotype. Directly developing frogs have evolved a derived life-history mode where the tadpole stage has been deleted and embryos develop directly into the adult bauplan. Embryonic development in E. coqui is classified into 15 stages (TS 1–15; 1 = oviposition / 15 = hatching). Serotonergic immunoreactivity was initially detected at TS 6 in the raphe nuclei in the developing rhombencephalon. At TS 7, immunopositive perikarya were observed in the paraventricular organ in the hypothalamus and reticular nuclei in the hindbrain. Development of the serotonergic system was steady and gradual during mid-embryogenesis. However, starting at TS 13 there was a substantial increase in the number of serotonergic neurons in the paraventricular, raphe, and reticular nuclei, a large increase in the number of varicose fibers, and a differentiation of the reticular nuclei in the hindbrain. Consequentially, E. coqui displayed a well-developed central serotonergic system prior to hatching (TS 15). In comparison, the serotonergic system in metamorphic frogs typically starts to develop earlier but the surge of development that transpires in this system occurs post-embryonically, during metamorphosis, and not in the latter stages of embryogenesis, as it does in E. coqui . Overall, the serotonergic development in E. coqui is similar to the other vertebrates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47526/1/429_2005_Article_22.pd

Hypothalamic centers and innervation of the hypophysis in the Atlantic salmon (Salmo salar) and the rainbow trout (Salmo gairdneri)

International audienc

Dynamics in immunocytochemical labelling of granules in the gonadotrops of the African catfish Clarias gariepinus, as a function of induced release

The gonadotropic hormone (GTH) plays a regulative role in the reproductive cycle of teleosts. GTH-cell activity is under dual hypothalamic control i.e. stimulation by the peptide gonadotropin releasing hormone (GnRH) and inhibition by dopamine. Immunolabelling gives a specific localization of GTH in the granules of gonadotrops in the pituitary of the African catfish. Recently it has been shown for the pancreas, that the intensity of the labelling of secretory granules varies under different experimental conditions. In the present study a possible relationship between induced release of GTH and immunocytochemical labbeling of granules in catfish gonadotrops was investigated

Hypothalamo-hypophysial relations in amphibian larvae

The results of studies on the differentiation of the preoptic nucleus and of experiments regarding the effects of propylthiouracil and extirpation of the preoptic area demonstrate that in Xenopus laevis tadpoles a thyrotropin-releasing factor (TRF) is formed in peptidergic cells in the dorsal part of the preoptic nucleus. The differentiation of this nucleus depends on thyroid hormones, but at the same time these hormones inhibit the activity of the TRF cells. Young larvae of X. laevis acquire the ability to adapt themselves to a white background simultaneously with the appearance of aminergic neurosecretory centers in the caudal hypothalamus. During prometamorphosis these centers comprise a paraventricular organ (PVO), a nucleus infundibularis, fiber tracts to the telencephalon and to the pars intermedia of the adenohypophysis, and a nucleus in the caudalmost part of the dorsal tuber cinereum. The PVO consists of sensory nerve cells and cells secreting products into the cerebrospinal fluid; the infundibular nucleus contains numerous liquor-contacting neurons. The aminergic neurosecretory cells contain catecholamines such as dopamine. Depletion of these cells by reserpine leads to a dispersion of melanin granules in the skin melanophores. It is believed that among the functions of the aminergic neurosecretory centers is the production of a melanotropin-inhibiting factor. In the ventral tuber cinereum of X. laevis, neurosecretory cells are situated that are neither peptidergic nor aminergic. They are more active in adult animals than in tadpole

Premalignant epithelial disorders of the vulva: squamous vulvar intraepithelial neoplasia, vulvar Paget's disease and melanoma in situ

No standard screening programs exist to detect vulvar carcinoma or its precursor lesions, and therefore gynecologists, dermatologists and other healthcare providers in this field should be aware of the clinical features, behavior and management of the different existing premalignant vulvar lesions, squamous vulvar intraepithelial neoplasia (VIN), vulvar Paget's disease and melanoma in situ. In 2004, a new classification for squamous VIN was introduced by the International Society for the Study of Vulvar Disease, subdividing squamous VIN into the HPV-related usual type, and into differentiated type, which is associated with lichen sclerosus. This review describes the relevant aspects of squamous VIN, vulvar Paget's disease and melanoma in situ, its epidemiological characteristics, diagnosis, management and malignant potential