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Background: Immediate lymphatic reconstruction (ILR), performed at the time of axillary lymph node dissection (ALND), has demonstrated promising reductions in breast cancer-associated lymphedema. However, questions remain over the effects of adjuvant therapies on the continued patency of the lymphaticovenous anastomosis. Our study aimed to assess lymphographic outcomes, including ICG pattern and LVB patency, in patients at high risk for breast cancer-associated lymphedema following axillary ILR., Methods: Baseline ICG lymphography studies performed during ILR of 15 patients were compared to repeat ICG studies obtained during second-stage breast reconstructive procedures to assess for changes in lymphatic flow patterns through the at-risk arm and transit into the axilla., Results: All 15 patients in this study demonstrated linear lymphatic flow in baseline lymphography. Repeat lymphographic studies showed linear lymphatic transit in 12/15 patients. Of these 12 patients, 10 received chemotherapy, and all 12 received post-mastectomy radiation (PMRT). Dermal backflow patterns were recorded in 3/15 patients. All 3 patients received chemotherapy and 2/3 underwent PMRT. Additionally, repeat ICG studies of 7/12 lymphedema-free patients demonstrated clear visualization of linear ICG flow from the lymphatics of the arm into the axilla., Conclusion: We have demonstrated that ICG lymphography can be implemented as a postoperative tool to assess lymphatic function in patients who have undergone ILR in the axilla. Repeat ICG studies in the majority of patients demonstrated linear ICG flow similar to baseline studies. Additionally, ICG flow patterns through the axilla in repeat lymphography provided visual evidence supporting sustained LVB patency, despite axillary irradiation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Metabolism of polyunsaturated fatty acids results in the formation of hydroxylated fatty acids that can be further oxidized by dehydrogenases, often resulting in the formation of electrophilic, α,β-unsaturated ketone containing fatty acids. As electrophiles are associated with redox signaling, we sought to investigate the metabolism of the oxo-fatty acid products in relation to their double bond architecture. Using an untargeted liquid chromatography mass spectrometry approach, we identified mono- and di-saturated products of the arachidonic acid-derived 11-oxoeicosatetraenoic acid (11-oxoETE) and mono-saturated metabolites of 15-oxoETE and docosahexaenoic acid-derived 17-oxodocosahexaenoinc acid (17-oxoDHA) in both human A549 lung carcinoma and umbilical vein endothelial cells. Notably, mono-saturated oxo-fatty acids maintained their electrophilicity as determined by nucleophilic conjugation to glutathione while a second saturation of 11-oxoETE resulted in a loss of electrophilicity. These results would suggest that prostaglandin reductase 1 (PTGR1), known only for its reduction of the α,β-unsaturated double bond, was not responsible for the saturation of oxo-fatty acids at alternative double bonds. Surprisingly, knockdown of PTGR1 expression by shRNA confirmed its participation in the formation of 15-oxoETE and 17-oxoDHA mono-saturated metabolites. Furthermore, overexpression of PTGR1 in A549 cells increased the rate and total amount of oxo-fatty acid saturation. These findings will further facilitate the study of electrophilic fatty acid metabolism and signaling in the context of inflammatory diseases and cancer where they have been shown to have anti-inflammatory and anti-proliferative signaling properties., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Adipose tissue-derived stromal cells (ASCs) are increasingly being studied for their usefulness in regenerative medicine. However, limited life span and donor-dependent variation of primary cells such as ASCs present major hurdles to controlled and reproducible experiments. We therefore aimed to establish immortalized ASC cell lines that provide steady supply of homogeneous cells for in vitro work while retain essential features of primary cells. To this end, combinations of human telomerase reverse transcriptase (hTERT), murine Bmi-1, and SV40 large T antigen (SV40T) were introduced by lentiviral transduction into ASCs. The resulting cell lines ASC(hTERT), ASC(Bmi-1), ASC(Bmi-1+hTERT) and ASC(SV40T+hTERT) were tested for transgene expression, telomerase activity, surface immunomarkers, proliferation, osteogenic and adipogenic differentiation, karyotype, tumorigenicity, and cellular senescence. All cell lines have maintained expression of characteristic surface immunomarkers, and none was tumorigenic. However, ASC(Bmi-1) had limited replicative potential, while the rapidly proliferating ASC(SV40T+hTERT) acquired chromosomal aberrations, departed from MSC phenotype, and lost differentiation capacity. ASC(hTERT) and ASC(hTERT+Bmi-1), on the other hand, preserved all essential MSC features and did not senesce after 100 population doublings. Notably, a subpopulation of ASC(hTERT) also acquired aberrant karyotype and showed signs of transformation after long-term culture. In conclusion, hTERT alone was sufficient to extend the life span of human ASC, but ASC(hTERT) are prone to transformation during extensive subculturing. The combination of Bmi-1 and hTERT successfully immortalized human ASCs without significantly perturbing their phenotype or biological behavior., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Antigen-presenting cells (APCs) are multifunctional components of the immune defense system. In this study, murine APCs were used as biosensors to detect immunologically active components of bovine milk and colostrum. By measuring changes in cell surface protein markers [major histocompatibility complex II, cluster designation (CD)40, CD86] and cytokines (tumor necrosis factor-alpha and interleukin-10) associated with APC activation, we identified a number of compounds that are immunoactive. The mouse macrophage cell line MH-S offered a simple and robust target for identification of immunoactives. The assay was shown to be adaptable for measuring immunoenhancing or immunosuppressive substances. Large-scale screening of milk extracts using this bioassay has the potential to identify substances that could be developed into nutraceuticals or pharmaceutical-grade immunotherapeutics.

PURPOSE: Various medical conditions, infectious agents, sexual, and hormonal factors have been investigated in relation to prostate cancer risk. Given inconsistent results these factors were examined in this study.METHODS: This population-based case-control study was conducted in northeastern Ontario from 1995 to 1999. Cases (n = 760), aged 45 to 84 at the time of diagnosis, were identified through the Ontario Cancer Registry and diagnosed between January 1995 and December 1998. Controls (n = 1,634) were age-frequency matched and were selected from the northeastern Ontario population using published telephone listings. Mail and telephone questionnaires were used for data collection. Logistic regression was used to investigate risk associated with: 1) particular medical conditions and 2) hormonal and sexual factors. Cases were subdivided into those with symptoms of prostate disease and those with few or no such symptoms.RESULTS: Symptomatic cases who reported a history of venereal disease (age-adjusted odds ratio (OR) = 2.11, 95% confidence interval (CI) 1.18-3.80) and vasectomy (age-adjusted OR = 1.49, 95% CI 1.14-1.95) were at significantly increased risk of prostate cancer. Asymptomatic cases who reported a check-up at least once a year were at increased risk (age-adjusted OR = 1.46, 95% CI 1.08-1.98). Asymptomatic and symptomatic cases who reported a history of prostate cancer in a first degree relative were at increased risk (age-adjusted OR = 2.41, 95% CI 1.64-3.54; age-adjusted OR = 3.18, 95% CI 2.28-4.45, respectively). Symptomatic cases with a history of urinary tract infection were at non-significantly increased risk (age-adjusted OR = 1.31, 95% CI 0.98-1.76). Heart disease, mumps, allergies, and height were generally not associated with prostate cancer.CONCLUSIONS: A history of venereal disease, family history of prostate cancer, and vasectomy were positively associated with prostate cancer. Further investigation of selected medical conditions, sexual, and hormonal factors in prostate cancer development is warranted.

Since the recent extensive domestication and farming of deer in New Zealand, tuberculosis (Tb) has presented a major health issue in farmed herds. The spectrum of disease pathology and immune reactivity in this naturally infected species represents a potentially valuable large animal model for the study of the underlying immunological and pathological mechanisms involved in Mycobacterium bovis infection and its spread. A combination of laboratory assays for the detection of tuberculosis in deer is described. Domesticated deer are genetically diverse and their exposure to natural variations in environmental conditions results in a spectrum of immune responses and pathology of Tb, similar to that found in man. The model has special relevance to the study of host responses to tuberculosis in immunocompromised individuals, particularly those in the third world. Elucidation of the mechanisms involved in immune responses to Tb in deer will facilitate the development of vaccines and improved diagnostic assays for Tb in man.