Different Growth Patterns of Canine Prostatic Carcinoma Suggests Different Models of Tumor-Initiating Cells.

Controversies remain regarding the cell type from which human prostate cancer originates, and many attempts have been made to identify the cellular origin of canine prostate cancer but without definitive proof. This study aims to evaluate the expression of luminal (androgen receptor [AR], cytokeratin [CK]8/18) and basal (CK14, CK5) cell markers in different histologic subtypes of canine prostatic carcinoma (PC) and to suggest the most likely tumor-initiating cells. Normal prostates (n = 8) were characterized by AR+CK8/18+ luminal cells and few CK5+ basal cells, while CK14 was absent. Similar pattern was observed in all 35 prostates with benign prostatic hyperplasia, except few scattered CK14+ basal cells in 13 samples (37.14%). AR was localized in the nucleus of both normal and hyperplastic cells. In 34 samples of PC, the following growth patterns were identified: cribriform (44.12%), solid (32.35%), small acinar/ductal (20.59%), and micropapillary (2.94%). Most PCs expressed AR and CK8/18, while CK5 and CK14 expression was observed in 25% and 20% of cases, respectively. AR revealed a variable intracellular distribution, both nuclear and cytoplasmic. Solid PC was characterized by an undifferentiated or aberrant phenotype with a reduced expression of AR and CK8/18, increased number of CK14+ cells, and 7 antigen expression patterns. This study demonstrated a predominance of differentiated luminal cell types in canine prostatic tumors, although the role of basal cells in prostate carcinogenesis should also be considered. Moreover, few scattered CK5+ cells in AR+CK8/18+ tumors identified the existence of intermediate cells, from which neoplastic transformation may alternatively commence.

Immunohistochemical characterization of phagocytic immune cell infiltration into different adipose tissue depots of dairy cows during early lactation.

The present study aimed to investigate whether phagocytic immune cells infiltrate into bovine adipose tissue (AT) and to study the effects of lactation and conjugated linoleic acid (CLA) supplementation on the invasion of phagocytic immune cells into different s.c. and visceral (v.c.) fat depots of primiparous dairy cows during the first 105 d in milk (DIM). German Holstein-Friesian cows (HF; n = 25) with a mean body condition score of 3.0 were divided into a control (CON) and a CLA group. From 1 DIM until sample collection, CLA cows were fed 100 g of CLA supplement/d (about 6% of c9,t11 and t10,c12 isomers each), whereas the CON cows received 100 g/d of a fatty acid mixture instead of CLA. The CON cows (n = 5 each) were slaughtered at 1, 42, and 105 DIM, and the CLA cows (n = 5 each) were slaughtered at 42 and 105 DIM. Adipose tissues (n = 150) from 3s.c. (tailhead, withers, and sternum) and 3 v.c. (omental, mesenteric, and retroperitoneal) depots were sampled. In addition, s.c. tailhead biopsies were collected by repeated surgical biopsies (3 samplings within 7 wk; n = 36) from 12 nonpregnant, nonlactating Simmental heifers (SM; mean body condition score = 5.0) fed diets of varying energy density to compare the changes in phagocytic immune cell infiltration with early lactating cows. Immunohistochemical analyses of different fat depots revealed a low incidence of phagocytic immune cell infiltration in early lactating cows. The portion of infiltrating macrophages (CD68+) in a few positive AT samples of HF cows was slightly lower in s.c. than v.c. fat and was positively correlated with both empty body weight and adipocyte size. However, no differences with regard to DIM and CLA supplementation were observed in HF cows. Increased accumulation of phagocytic immune cells, albeit at low cell numbers, in nonpregnant, over-conditioned SM heifers might be related to larger adipocytes secreting higher amounts of chemoattractant adipokines compared with the early lactating cows. In conclusion, the extent of fatness in HF cows may not be high enough to stimulate significant infiltration of phagocytic cells in AT and, therefore, these immune cells might have no major role in the immunologic and metabolic adaptations of AT during early lactation.

Physiological and conjugated linoleic acid-induced changes of adipocyte size in different fat depots of dairy cows during early lactation.

The aim of this study was to investigate the effects of lactation and conjugated linoleic acid (CLA) supplementation on adipocyte sizes of subcutaneous (s.c.) and visceral (VC) fat depots in primiparous dairy cows during the first 105 d in milk (DIM). German Holstein heifers (n=25) were divided into a control (CON) and a CLA group. From 1 DIM until sample collection, CLA cows were fed 100g of CLA supplement/d (about 6% of c9,t11 and t10,c12 isomers each), whereas the CON cows received 100g of fatty acid mixture/d instead of CLA. The CON cows (n=5 each) were slaughtered at 1, 42, and 105 DIM, and the CLA cows (n=5 each) were slaughtered at 42 and 105 DIM. Adipose tissues from 3s.c. depots (tailhead, withers, and sternum) and from 3 VC depots (omental, mesenteric, and retroperitoneal) were sampled. Hematoxylin-eosin staining was done to measure adipocyte area (µm(2)). Retroperitoneal adipocyte sizes were mostly larger than adipocytes from the other sites, independent of lactation time and treatment. Significant changes related to duration of lactation were limited to retroperitoneal fat: adipocyte sizes were significantly smaller at 105 DIM than at 1 DIM in CON cows. Adipocyte sizes were decreased in s.c. depots from the tailhead at 105 DIM and from the sternum at 42 DIM in CLA versus CON cows, whereas for VC depots, adipocyte sizes were decreased in mesenteric fat at 42 and 105 DIM, and in omental and retroperitoneal fat, at 105 DIM in CLA versus CON cows. Within the CLA group, adipocyte sizes were smaller in the s.c. depot from the tailhead at 105 DIM than at 42 DIM. Adipocyte sizes and depot weights were significantly correlated in s.c. depots (r=0.795) in the CLA group and in retroperitoneal fat both in the CON (r=0.698) and the CLA (r=0.723) group. In conclusion, CLA-induced decreases in adipocyte size indicate lipolytic or antilipogenic effects of CLA, or both effects, on adipose tissue in primiparous dairy cows.

Diagnostic Utility of Cytokeratin-5 for the Identification of Proliferative Inflammatory Atrophy in the Canine Prostate.

Proliferative inflammatory atrophy (PIA), which is comprised of highly proliferative but atrophic prostate epithelial cells in association with chronic inflammation, is considered a risk lesion for prostate cancer in men, while its role in canine prostate carcinogenesis is still unknown. We evaluated the value of immunohistochemical labelling for the basal cell marker cytokeratin-5 (CK5) in identifying PIA lesions in 87 samples of formalin-fixed and paraffin wax-embedded canine prostate. Canine PIA showed cytological features identical to the human counterpart and in most cases was associated with chronic lymphoplasmacytic inflammation. PIA lesions were identified in a higher number of CK5-labelled slides (43 out of 87) compared with slides stained by haematoxylin and eosin (HE) (24 out of 87). This lesion was frequently present in normal, hyperplastic and neoplastic canine prostates, although it was underestimated on evaluation of HE-stained slides. Therefore, CK5 can be considered a useful basal cell marker with high sensitivity and specificity for PIA.

A retrospective analysis of 111 canine prostatic samples: histopathological findings and classification.

The purpose of this retrospective study is to evaluate the frequency and further characterize the pathological features of common and uncommon histological lesions in 111 canine prostatic samples. Benign prostatic hyperplasia, suppurative and non-suppurative prostatitis, and prostate cancer were observed individually or in combination in 45, 11, 68 and 50 samples, respectively. Six growth patterns of prostatic carcinoma were differentiated: papillary, cribriform, solid, small acinar/ductal, signet ring, mucinous. In a few cases, perineurial invasion and collagenous micronodules were observed. Lesions considered preneoplastic in men, such as high-grade prostatic intraepithelial neoplasia (HGPIN) and prostatic inflammatory atrophy (PIA), were observed in 27 and 21 histological samples, respectively. This study represents a detailed characterization of the different histological subtypes of canine prostate cancer. The awareness of the unusual patterns might be critical in avoiding diagnostic misinterpretation. The high prevalence of PIA and HGPIN underlines the reasonable chance of their detection in routine biopsy specimens.

Lactation driven dynamics of adiponectin supply from different fat depots to circulation in cows.

Adipose tissue (AT) depots are heterogeneous in terms of morphology and adipocyte metabolism. Adiponectin, one of the most abundant adipokines, is known for its insulin sensitizing effects and its role in glucose and lipid metabolism. Little is known about the presence of adiponectin protein in visceral (vc) and subcutaneous (sc) AT depots. We assessed serum adiponectin and adiponectin protein concentrations and the molecular weight forms in vc (mesenterial, omental, and retroperitoneal) and sc (sternum, tail-head, and withers) AT of primiparous dairy cows during early lactation. Primiparous German Holstein cows (n = 25) were divided into a control (CON) and a conjugated linoleic acid (CLA) group. From day 1 of lactation until slaughter, CLA cows were fed 100 g of a CLA supplement/d (approximately 6% of cis-9, trans-11 and trans-10, cis-12 isomers each), whereas the CON cows received 100 g of a fatty acid mixture/d instead of CLA. Blood samples from all animals were collected from 3 wk before calving until slaughter on day 1 (n = 5, CON cows), 42 (n = 5 each of CON and CLA cows), and 105 (n = 5 each of CON and CLA cows) of lactation when samples from different AT depots were obtained. Adiponectin was measured in serum and tissue by ELISA. In all AT depots adiponectin concentrations were lowest on day 1 than on day 42 and day 105, and circulating adiponectin reached a nadir around parturition. Retroperitoneal AT had the lowest adiponectin concentrations; however, when taking total depot mass into consideration, the portion of circulating adiponectin was higher in vc than sc AT. Serum adiponectin was positively correlated with adiponectin protein concentrations but not with the mRNA abundance in all fat depots. The CLA supplementation did not affect adiponectin concentrations in AT depots. Furthermore, inverse associations between circulating adiponectin and measures of body condition (empty body weight, back fat thickness, and vc AT mass) were observed. In all AT depots at each time, adiponectin was present as high (approximately 300 kDa) and medium (approximately 150 kDa) molecular weight complexes similar to that of the blood serum. These data suggest differential contribution of AT depots to circulating adiponectin.

Characterization of the dynamics of fat cell turnover in different bovine adipose tissue depots.

In many but not all high producing cows, the energy requirements for milk yield and maintenance exceed energy intake by voluntary feed intake during early lactation. Prioritizing milk secretion, body reserves mainly from adipose tissue are mobilized and imply an increased risk for metabolic diseases. Reducing the energy output via milk by decreasing the milk fat content through feed supplements containing conjugated linoleic acids (CLAs) may attenuate the negative energy balance during this period. In two separate trials, variables characterizing fat cell turnover were investigated in different subcutaneous and visceral fat depots from primiparous heifers (n = 25) during early lactation, and subcutaneous fat from non-lactating, over-conditioned heifers (n = 12) by immunohistochemistry. The portion of apoptotic adipocytes was consistently greater than that of proliferating cells and preadipocytes; the sporadically observed effects of CLA were limited to visceral fat. Lactating heifers had more apoptosis and less preadipocytes than non-lactating heifers.

The effect of selenium and vitamin E on the lymphocytes and immunoglobulin-containing plasma cells in the lymphoid organ and mucosa-associated lymphatic tissues of broiler chickens.

The present research has been designed to understand the effect of selenium and vitamin E on the lymphocyte and changes in the frequency of Ig-containing plasma cells in the lymphatic organ and ileum (representative organ for mucosa-associated lymphatic tissues) of different postnatal stages of Kasilla broiler chickens. A routine haematoxylin and eosin (H and E) stain were used to study the histology of the lymphocytic changes, and indirect immunoperoxidase staining method was performed for the study of the distributional and dynamical changes of the Ig-containing plasma cells within the lymphatic tissues and in the ileum of control broilers and in the broilers supplemented with different concentration of selenium and vitamin E in the diet. Histologically, the population of lymphocytes decreased in the lobules of the thymus, medulla of bursal follicles, splenic masses, lymphatic nodules of the cecal tonsil, and villi of the ilium in 0.1 mg and 0.5 mg selenium supplemented broilers in comparison with the control. The population of these cells was found to increase in 150 mg and 300 mg vitamin E supplemented chickens in the present study. In the spleen IgG- and the IgM-containing plasma cells were more than IgA-containing plasma cells. In contrast, in the cecal tonsil and ileum IgA-containing plasma cells were more than IgG- and IgM-containing plasma cells. The frequency of these immunopositive cells were decreased in 0.1 mg and 0.5 mg selenium supplementated chickens, and increased their frequency in the chickens supplemented with 150 mg and 300 mg vitamin E. In the spleen the frequency of IgM-containing plasma cells and both in the cecal tonsil and ileum, the IgG-containing plasma cells were more decreased by selenium supplementation which restored in their population by vitamin E supplementation.