Previous studies of fatty acids and breast cancer risk have shown mixed results, which may be due in part to tumor heterogeneity. Prior research has also illustrated an important role of specific fatty acids in immune regulation, T cell function, and inflammation, indicating that the effects of specific fatty acids on breast cancer risk may vary by tumor expression of immuno-inflammatory markers. We therefore aimed to evaluate the relationships between prediagnostic erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers (CD4, CD8, CD20, CD163, COX-2) and fatty acid synthase (FAS).
We conducted a matched case-control study nested within the Nurses\' Health Study II (n = 235 cases and 235 controls). Blood samples were collected from 1996 to 1999. Tumor tissue blocks were collected for cases diagnosed after blood collection and through 2006. Unconditional nominal polytomous logistic regression adjusted for matching factors and potential confounders was used to assess whether associations between fatty acids and breast cancer risk varied by tumor expression subtype, ascertained via immunohistochemistry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated separately by tumor expression subtype using unconditional logistic regression.
Associations between fatty acids and breast cancer risk did not vary substantially by tumor CD4, CD20, CD163, or COX-2. However, n-3 polyunsaturated fatty acids (PUFAs) were inversely associated with CD8low but not CD8high cancers (CD8low ORT3 vs T1 = 0.45, 95% CI 0.23-0.87, Ptrend = 0.02; CD8high ORT3 vs T1 = 1.19, 95% CI 0.62-2.26, Ptrend = 0.62; Phet = 0.04). n-6 PUFAs were suggestively inversely associated with CD8high but not CD8low cancers (CD8high ORT3 vs T1 = 0.61, 95% CI 0.32-1.14, Ptrend = 0.11; CD8low ORT3 vs T1 = 1.63, 95% CI 0.87-3.04, Ptrend = 0.12; Phet = 0.02). Trans fatty acids were positively associated with FAShigh but not FASlow tumors (FAShigh ORT3 vs T1 = 2.94, 95% CI 1.46-5.91, Ptrend = 0.002; FASlow ORT3 vs T1 = 0.99, 95% CI 0.52-1.92, Ptrend = 0.97; Phet = 0.01).
Results indicate that the effects of n-3 PUFAs, n-6 PUFAs, and trans fatty acids on breast cancer risk may vary by tumor tissue expression subtypes. Findings suggest potential immuno-modulatory and FAS-mediated mechanisms.

Hodgkin lymphoma (HL) represents ~11% of all lymphoma cases. This disease occurs in young adults, but also affects people over 55 years of age. Despite the fact that >80% of all newly diagnosed patients under 60 will achieve a sustained complete response (CR), 5%-10% of HL patients are refractory to initial treatment and 10%-30% of patients will eventually relapse after an initial CR. The treatment recommendation for primary refractory or relapsed HL patients is salvage therapy followed by high-dose chemotherapy and autologous stem cell transplantation. Following this approach, a significant part will still relapse at any moment. Thus, further research and new drugs or combinations are required. Overexpression of COX-2 has been associated with poor prognosis in relapse/refractory HL patients, so it could be a potential therapeutic target in HL. For this purpose, several drugs may have a role: specific COX-2 inhibitors such as celecoxib or other anti-inflammatory drugs such as lenalidomide may further inhibit lipopolysaccharide-mediated induction of COX-2. Moreover, lenalidomide and COX-2 inhibitors (celecoxib) have been tested in solid tumors with encouraging results. We present a case of a young female diagnosed with a heavily pretreated HL nodular sclerosis subtype who, after failing six treatment lines, only achieved clinical and radiological CR after six cycles of lenalidomide/celecoxib that resulted in an event-free survival of 22 months. We explain the rationale of using this chemotherapy regimen and our patient follow-up.

Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli\'s recent preclinical studies that 1. \"in vitro\" metformin modulates the ACC cell model H295R and 2. \"in vivo\" metformin inhibits tumor growth in a xenograft model as confirmed by a significant reduction of Ki67 [1]. Here we report on our prior clinical case study that provides proof of concept for Poli\'s studies. We were requested to perform morphoproteomic analysis to further define the biology of, and raise targeted therapeutic options, for a case of post-treatment and chemoresistant ACC metastatic to the liver and the lung. Profiling the patient\'s ACC from the liver resulted in the recommendation of metformin as a maintenance therapy, which was supported by biomedical data analysis. The patient remains on maintenance therapy with metformin and melatonin and is free of disease some 7 years post diagnosis, thus underscoring the recommendation for clinical trials employing these therapeutic agents.

Blastic plasmocytoid dendritic cell neoplasm is characterized by aggressive behavior with a tendency for systemic dissemination and a predilection for skin, lymph nodes, soft tissues, peripheral blood, or bone marrow. It usually occurs in elderly patients with a mean age between 60 and 70 years. Despite initial response to chemotherapy, the disease regularly relapses with a short median overall survival. Better outcomes have been reported with high-dose acute leukemia-like induction chemotherapy followed by consolidation with allogeneic hematopoietic stem cell transplantation. However, elderly patients are not candidates for intensive therapy or allogeneic stem cell transplantation. So, new active and tolerable drugs are needed. Our case illustrates that one cycle of lenalidomide and celecoxib provides at least a partial cutaneous and hematologic response, but this regimen was discontinued due to toxicity and followed by a consolidation/maintenance phase with azacitidine, thus achieving a final complete response with a much higher than expected progression-free and overall survival in an elderly patient with comorbidities. This information may be useful in the design of treatment approaches for elderly patients with blastic plasmocytoid dendritic cell neoplasm. However, it should be confirmed in clinical trials as well as by optimizing the induction and extending the consolidation/maintenance period to avoid early relapses after discontinuation and improve progression-free survival.

OBJECTIVE: Cyclooxygenase 2 (COX-2) with the resulting prostaglandin E2 (PGE2) is linked to increased risk of human breast cancer (BC). The aim of this study was to determine COX-2 169C>G and 8473T>C gene polymorphisms and PGE2 level at various stages of BC clarifying the role of COX-2 gene polymorphism and PGE2 in relation to BC.
METHODS: The study population comprised 160 women at different stages of BC and 150 gender- and age-matched healthy control subjects. Plasma PGE2 was measured by ELISA, the COX-2 gene polymorphisms were determined using PCR-RFLP.
RESULTS: The variant alleles COX-2 169G and 8473C were significantly associated with BC susceptibility [OR=3.1, 95% CI (2.2-4.4), P<0.001 for 169C>G and OR=1.74, 95%CI (1.3-2.4), P=0.005 for 8473C]. However, both COX-2 gene polymorphisms were not associated with breast cancer stage. Plasma PGE2 levels were significantly increased in patients compared to the controls. In early and late stages of BC, there was a significant increase in the plasma PGE2 levels towards the presence of homozygous GG compared with homozygous CC (P<0.001) for 169 C>G, also towards the presence of CC than TT (P<0.001) for 8473T>C SNP.
CONCLUSIONS: The 169C>G and 8473T>C polymorphisms of the COX-2 gene were associated with the BC in Egyptian women. Furthermore, individuals with COX-2 169GG and 8473CC genotypes showed significant increase in plasma PGE2 levels. PGE2 levels may serve as a predictor of poor prognosis in patients with BC.

BACKGROUND: Discoid lupus erythematosus is a chronic inflammatory skin disorder presenting with scarring lesions that occur predominately on sun exposed areas of the face and scalp.
METHODS: A 22-year-old male was evaluated after presenting with reddish-purple, atrophic and erythematous plaques on the scalp, with loss of hair within the plaques. Biopsies for hematoxylin and eosin examination, direct immunofluorescence and immunohistochemistry analysis were performed. The hematoxylin and eosin staining demonstrated classic features of cutaneous lupus. Direct immunofluorescence revealed strong deposits of immunoglobulins IgG and IgM, fibrinogen and Complement/C3, present in 1) a shaggy pattern at the epidermal basement membrane zone, and 2) focal pericytoplasmic and perinuclear staining within epidermal keratynocytes. Immunohistochemisty staining revealed strongly positive staining with antibodies to cyclooxygenase-2, Zeta-chain-associated protein kinase 70, and HLA-DPDQDR in areas where the inflammatory infiltrate was predominant, as well as around dermal blood vessels and within the dermal extracellular matrix.
CONCLUSIONS: Noting the autoimmune nature of lupus and its strong inflammatory component, we present a patient with active discoid lupus erythematosus and strong expression of Zeta-chain-associated protein kinase 70, cyclo-oxygenase-2, and HLA-DPDQDR in the inflammatory areas. We suggest that these molecules may play a significant role in the immune response of discoid cutaneous lupus, possibly including 1) the biosynthesis of the prostanoids and 2) activation of the signaling cascade in response to T-lymphocyte receptor stimulation.