Breast Lipofilling Does Not Pose Evidence of Chronic Inflammation in Rats.

BACKGROUND: Laboratory reports on adipose tissue suggest that fat grafting to the breast may pose an oncologic risk. One possible reason for this is the theoretic chronic inflammation due to adipokynes released by grafted white adipose tissue (WAT). OBJECTIVES: The aim of this study was to analyze inflammatory activity in lipofilled breast through the use of proinflammatory markers. METHODS: Fifty-four paired-breasts of female rats were divided into 4 groups: control, sham, and breasts grafted with either autologous subcutaneous (SC) WAT or autologous omentum (OM). The WAT was prepared through centrifugation, and the grafting was performed with the use of 0.9-mm blunt-tip cannula. The rats were killed 8 weeks postoperatively, and their breasts were harvested for immunohistochemical staining for CD68-expressing macrophages, gene expression (real-time PCR) for monocyte chemoattractant protein 1 (MCP-1), F4/80, Cox-2, and IL-6. RESULTS: The weights of the rats that underwent a procedure differed from those of the unmanipulated control group (P < 0.01). The macrophage counts of CD68 differed only between breasts lipofilled with OM and control (P < 0.01). MCP-1, F4/80, and Cox-2 were similarly expressed among the groups (P = 0.422, P = 0.143, and P = 0.209, respectively). The expression of IL-6 differed between breast samples grafted with SC and OM WAT (P = 0.015), but not between samples of control and OM (P = 0.752), and control and SC (P = 0.056). CONCLUSIONS: No inflammation activity was identified in the microenvironment of lipofilled breasts, indicating that chronic inflammation does not seem to be triggered by the breast lipofilling procedure.

Assessment of the Cancer Risk of the Fat-Grafted Breast in a Murine Model.

Background: The results of experimental studies indicate that grafting of autologous adipose tissue may induce tumorigenesis at the recipient site, but clinical results do not support a carcinogenic effect of fat grafting to the breast. Objectives: The authors assessed cancer risk following transplantation of autologous fat into murine mammary tissue. Methods: In this animal study, mammary tissues from 54 breasts of 9 female rats were either grafted with autologous subcutaneous fat, grafted with autologous omental fat, or unmanipulated. Tissues were harvested and processed for histologic and immunohistochemical analyses, and the mRNA expression levels of specific genes were determined. Results: No atypia or changes in lobular structures were observed in lipofilled breasts compared with controls. The numbers of ductal cell layers and terminal ductal units were similar for lipofilled and control breasts. Macrophage concentrations also were similar for the 3 groups. The localization and magnitude of plasminogen activator inhibitor 1 were similar for lipofilled and unmanipulated breast tissue. The percentages of cells expressing Ki67 or estrogen receptor (ER) and the ER/Ki67 balance were similar for the 3 groups. Gene expression was not altered in lipofilled breasts, compared with controls. Conclusions: No theoretical risk of cancer was detected in the microenvironment of the lipofilled rat breast.

Unmanipulated native fat exposed to high-energy diet, but not autologous grafted fat by itself, may lead to overexpression of Ki67 and PAI-1.

BACKGROUND: Although its unclear oncological risk, which led to more than 20 years of prohibition of its use, fat grafting to the breast is widely used nowadays even for aesthetic purposes. Thus, we proposed an experimental model in rats to analyze the inflammatory activity, cellular proliferation and levels of Plasminogen Activator Inhibitor (PAI-1) in grafted fat, and in native fat exposed to high-energy diet in order to study the oncological potential of fat tissue. METHODS: Samples of grafted fat of rats on regular-energy diet were compared with paired samples of native fat from the same rat on regular-energy diet and on high-energy diet in a different time. Analysis involved microscopic comparisons using hematoxylin-eosin staining, immunohistochemistry with anti-CD68-labelled macrophages, and gene expression of Ki-67 and PAI-1. RESULTS: Hematoxylin-eosin staining analyses did not find any atypical cellular infiltration or unusual tissue types in the samples of grafted fat. The inflammatory status, assessed through immunohistochemical identification of CD68-labelled macrophages, was similar among samples of native fat and grafted fat of rat on regular-energy diet and of native fat of rats on high-energy diet. Real-time PCR revealed that high-energy diet, but not fat grafting, leads to proliferative status on adipose tissue (overexpression of ki-67, p = 0.046) and raised its PAI-1 levels, p < 0.001. CONCLUSION: While the native adipose tissue overexpressed PAI-1 and KI67 when exposed to high-energy diet, the grafted fat by itself was unable to induce cellular proliferation, chronic inflammatory activity and/or elevation of PAI-1 levels.

Low-power laser irradiation fails to improve liver regeneration in elderly rats at 48 h after 70 % resection.

The liver regeneration is an important clinical issue after major hepatectomies. Unfortunately, many organs (including the liver) exhibit age-related impairments regarding their regenerative capacity. Recent studies found that low-power laser irradiation (LPLI) has a stimulatory effect on the liver regeneration process. However, its effects in elderly remain unknown. Thus, this study aimed to investigate the main molecular mechanisms involved in liver regeneration of partially hepatectomized elderly rats exposed to LPLI. The effects of 15 min of LPLI (wavelength of 632.8 nm; fluence of 0.97 J/cm(2); total energy delivered of 3.6 J) were evaluated in hepatectomized elderly Wistar male rats. Afterwards, through immunoblotting approaches, the protein expression and phosphorylation levels of hepatocyte growth factor (HGF), Met, Akt and Erk 1/2 signaling pathways as well as the proliferating cell nuclear antigen (PCNA) were investigated. It was observed that LPLI was not able to improve liver regeneration in elderly rats as evidenced by the lack of improvement of HGF and PCNA protein expression or phosphorylation levels of Met, Akt and Erk 1/2 in the remnant livers. In sum, this study demonstrated that the main molecular pathway, i.e. HGF/Met → Akt and Erk 1/2 → PCNA, involved in the hepatic regeneration process was not improved by LPLI in elderly hepatectomized rats, which in turn rules out LPLI as an adjuvant therapy, as observed in this protocol of liver regeneration evaluation (i.e. at 48 h after 70 % resection), in elderly.

Liver regeneration following partial hepatectomy is improved by enhancing the HGF/Met axis and Akt and Erk pathways after low-power laser irradiation in rats.

A simple, easy, and safe procedure aiming to improve liver regeneration could be of great clinical benefit in critical situations such as major hepatectomy, trauma, or hemorrhage. Low-power laser irradiation (LPLI) has come into a wide range of use in clinical practice by inducing regeneration in healthy and injured tissues. However, the effect of LPLI on the process of liver regeneration, especially those related to the molecular mechanisms, is not fully understood. Thus, the aim of the present study was to investigate the main molecular mechanisms involved in liver regeneration of partially hepatectomized rats exposed to LPLI. We used Wistar male rats, which had their remaining liver irradiated or not with LPLI (wavelength of 632.8 nm and fluence of 65 mW/cm(2)) for 15 min after a 70% hepatectomy. We subsequently investigated hepatocyte growth factor (HGF), Met, Akt, and Erk 1/2 signaling pathways through protein expression and phosphorylation analyses along with cell proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67) using immunoblotting and histological studies. Our results show that LPLI can improve liver regeneration as shown by increased HGF protein expression and the phosphorylation levels of Met, Akt, and Erk 1/2 accompanied by higher levels of the PCNA and Ki-67 protein in the remnant livers. In summary, our results suggest that LPLI may play a clinical role as a simple, fast, and easy-to-perform strategy in order to enhance the liver regenerative capacity of a small liver remnant after hepatectomy.

Correlation between thymidylate synthase protein expression and gene polymorphism with clinicopathological parameters in colorectal carcinoma.

5-Fluorouracil (5-FU) represents the basis of chemotherapy for colorectal carcinoma, inhibiting thymidylate synthase (TS), an essential enzyme for DNA replication. Previous studies have associated high TS protein expression by tumor cells with poor outcome of patients with colorectal carcinoma, but others have refuted these findings. In view of the potential role of TS as predictive parameter and the lack of consensus in the literature, the present study compared 2 methods: protein expression and gene polymorphism, correlating them with clinicopathological findings. Immunohistochemical detection of TS in tumor cells and detection of gene polymorphism in the blood were performed in 32 patients with colorectal carcinoma treated with 5-FU. No correlation was found between TS protein expression and gene polymorphism. Neither method correlated with survival, tumor staging, and tumor histological grading. This result possibly reflects a complex tumor response to 5-FU therapy, where TS is just one of the involved proteins.

Relationship of age to outcome and clinicopathologic findings in men submitted to radical prostatectomy

OBJECTIVE: It is controversial whether age is associated with higher grade and worse outcome. Some studies have not found age to be related to outcome nor younger age to be associated with better response to therapy. MATERIALS AND METHODS: The study population consisted of 27 patients aged 55 years or younger and 173 patients 56 years or older submitted to radical prostatectomy. The variables studied were preoperative PSA, time to PSA progression following radical prostatectomy and pathologic findings in surgical specimens: Gleason score, Gleason predominant grade, positive surgical margins, tumor extent, extraprostatic extension (pT3a), and seminal vesicle invasion (pT3b). RESULTS: Comparing patients aged 55 years or younger and 56 years or older, there was no statistically significant difference for all variables studied: preoperative PSA (p = 0.4417), Gleason score (p = 0.3934), Gleason predominant grade (p = 0.2653), tumor extent (p = 0.1190), positive surgical margins (p = 0.8335), extraprostatic extension (p = 0.3447) and seminal vesicle invasion (p > 0.9999). During the study period, 44 patients (22 percent) developed PSA progression. No difference was found in the time to biochemical progression between men aged 55 years or younger and 56 years or older. CONCLUSION: Our findings suggest that age alone do not influence the biological aggressiveness of prostate cancer.

Relationship of age to outcome and clinicopathologic findings in men submitted to radical prostatectomy.

OBJECTIVE: It is controversial whether age is associated with higher grade and worse outcome. Some studies have not found age to be related to outcome nor younger age to be associated with better response to therapy. MATERIALS AND METHODS: The study population consisted of 27 patients aged 55 years or younger and 173 patients 56 years or older submitted to radical prostatectomy. The variables studied were preoperative PSA, time to PSA progression following radical prostatectomy and pathologic findings in surgical specimens: Gleason score, Gleason predominant grade, positive surgical margins, tumor extent, extraprostatic extension (pT3a), and seminal vesicle invasion (pT3b). RESULTS: Comparing patients aged 55 years or younger and 56 years or older, there was no statistically significant difference for all variables studied: preoperative PSA (p = 0.4417), Gleason score (p = 0.3934), Gleason predominant grade (p = 0.2653), tumor extent (p = 0.1190), positive surgical margins (p = 0.8335), extraprostatic extension (p = 0.3447) and seminal vesicle invasion (p > 0.9999). During the study period, 44 patients (22%) developed PSA progression. No difference was found in the time to biochemical progression between men aged 55 years or younger and 56 years or older. CONCLUSIONS: Our findings suggest that age alone do not influence the biological aggressiveness of prostate cancer.