The effects of jasmonates on the proliferation of human prostate cancer cell lines in culture

Jasmonic acid (JA), cis-Jasmone (CJ), and Methyl jasmonate (MJ), belong to a family of plant stress hormones known as the jasmonates. In plants, these compounds function as activators of cellular responses to diverse situations including cell death. Proliferation and cytotoxicity assays showed that the jasmonates inhibited the proliferation of the prostate cancer cell lines (PC-3 and DU-145), cultured in vitro. In addition, the type of inhibition exhibited by these agents was analyzed using flow cytometry (BrdU assay and Annexin V-FITC/PI staining) and fluorescence microscopy. The mechanism of inhibition was studied using 5-lipoxygenase enzyme. All agents (CJ, JA and MJ) inhibited proliferation of the cells in dose- and kinetic-dependent manners. All the assays confirmed that the inhibition was through the induction of apoptosis and that the mechanism of inhibition may involve the 5-lipoxygenase pathway. The results indicated a potential role for these compounds in the treatment of human prostate cancer

Unexplained pancytopenia in acute myeloid leukemia treatment

Certain histopathological findings have been described in acute myeloid leukemia (AML) patients during treatment that define the hematologic outcomes. Such entities as bone marrow necrosis and hemophagocytic lymphohistiocytosis have been reported. These often result in severe pancytopenia

Inhibition of expression of anti-apoptotic protein Bcl-2 and induction of cell death in radioresistant human prostate adenocarcinoma cell line (PC-3) by methyl jasmonate

Hormone refractory human prostate cancer cell lines are known to be radioresistant, a feature attributed to their ability to induce anti-apoptotic proteins of the Bcl-2 family when exposed to radiation. We investigated whether pro-apoptotic compounds such as methyl jasmonate, a plant stress hormone, can counteract the radiation-induced anti-apoptotic mechanism in a human prostate cancer cell line PC-3. Significant (p \u3c 0.05) increase in cytotoxicity was observed in the combined treatment groups compared to single treatments with methyl jasmonate or γ-radiation. Treatment of irradiated PC-3 cells with methyl jasmonate resulted in suppression of anti-apoptotic Bcl-2 protein and elevation of caspase-3 activity. Our results showed increased apoptosis in the combined treatment group as compared to the irradiated group or the untreated control. In summary, methyl jasmonate suppressed the radiation-induced Bcl-2 expression and enhanced the radiation sensitivity of human prostate cancer cells. © 2008 Elsevier Ireland Ltd. All rights reserved

Primary Extranodal Diffuse Large B-Cell Lymphoma of the Prostate: A Case Report

We report a case of primary diffuse large B-cell lymphoma of the prostate in a 54-year-old Caucasian male who presented with urinary retention and benign prostatic hyperplasia. We discuss the rare presentation of this disease and its clinicopathologic features and review the literature for up-to-date information on the diagnosis and clinical management. Despite the low incidence of lymphoma involving the prostate gland, it should always be considered as part of the differential diagnosis in cases of prostate gland enlargement with urinary tract obstructive symptoms resistant to medical therapy. Treatment modalities for this rare disease are also discussed

Dynamics of the interaction of human IgG subtype immune complexes with cells expressing R and H allelic forms of a low-affinity Fcγ receptor CD32A

CD32A, the major phagocytic FcγR in humans, exhibits a polymorphism in the ligand binding domain. Individuals homozygous for the R allelic form of CD32A (CD32AR allele) are more susceptible to bacterial infections and autoimmune diseases as compared with H allelic CD32A (CD32AH) homozygous and CD32AR/H heterozygous individuals. To understand the mechanisms behind this differential susceptibility, we have investigated the dynamics of the interaction of these allelic forms of CD32A when they are simultaneously exposed to immune complexes (IC). Binding studies using Ig fusion proteins of CD32A alleles showed that the R allele has significantly lower binding not only to human IgG2, but also to IgG1 and IgG3 subtypes. Competition assays using purified molecules demonstrated that CD32AH-Ig outcompetes CD32AR-Ig for IC binding when both alleles simultaneously compete for the same ligand. CD32AH-Ig blocked the IC binding mediated by both the allelic forms of cell surface CD32A, whereas CD32A R-Ig blocked only CD32AR and was unable to cross-block IC binding mediated by CD32AH. Two-dimensional affinity measurements also demonstrated that CD32AR has significantly lower affinity toward all three subtypes as compared with CD32AH. Our data suggest that the lower binding of CD32AR not only to IgG2 but also to IgG1 and IgG3 might be responsible for the lack of clearance of IC leading to increased susceptibility to bacterial infections and autoimmune diseases. Our data further suggests that in humans, inflammatory cells from CD32AR/H heterozygous individuals may predominantly use the H allele to mediate Ab-coated target cell binding during phagocytosis and Ab-dependent cellular cytotoxicity, resulting in a phenotype similar to CD32AH homozygous individuals. Copyright © 2009 by The American Association of Immunologists, Inc

Effective Immunotherapy in Bone Marrow Metastatic Melanoma Presenting with Disseminated Intravascular Coagulopathy

Malignant melanoma is responsible for the majority of skin cancer deaths and is increasing in prevalence. Bone marrow (BM) involvement by melanoma is rare in the absence of widespread visceral disease. Here, we report the case of a 30-year-old female who presented to the hospital with back pain, low-grade fever, and easy bruising. She was found to be bicytopenic and in disseminated intravascular coagulopathy (DIC). Surprisingly, BM biopsy showed extensive involvement by metastatic malignant melanoma in the absence of visceral or brain metastasis. The unique presentation of this case and the challenge of management of a potentially treatable cancer in a critically ill patient are discussed, alongside a review of published cases of metastatic melanoma in the BM and an exploration of currently available treatment options. The excellent response of our patient to combined immune checkpoint inhibitors has yet to be paralleled in the available literature

Apixaban for treatment of confirmed heparin-induced thrombocytopenia: a case report and review of literature

Abstract Background Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening condition caused by the binding of platelet-activating antibodies (IgG) to multimolecular platelet factor 4 (PF4)/heparin complexes because of heparin exposure. The by-product of this interaction is thrombin formation which substantially increases the risk of venous and/or arterial thromboembolism. Currently, only one anticoagulant, argatroban, is United States Food and Drug Administration-approved for management of HIT; however, this agent is expensive and can only be given by intravenous infusion. Recently, several retrospective case-series, case reports, and one prospective study suggest that direct oral anticoagulants (DOACs) are also efficacious for treating HIT. We further review the literature regarding current diagnosis and clinical management of HIT. Case presentation A 66-year-old male patient developed HIT beginning on day 5 post-cardiovascular surgery; the platelet count nadir on day 10 measured 16 × 109/L. Both the PF4-dependent ELISA and Serotonin-release assay were strongly positive. Despite initial anticoagulation with argatroban (day 6), the patient developed symptomatic Doppler ultrasound-documented bilateral lower extremity deep vein thrombosis on day 14 post-surgery. The patient was transitioned to the DOAC, apixaban, while still thrombocytopenic (platelet count 108) and discharged to home, with platelet count recovery and no further thrombosis at 3-month follow-up. Conclusions We report a patient with serologically confirmed HIT who developed symptomatic bilateral lower limb deep vein thrombosis despite anticoagulation with argatroban. The patient was switched to oral apixaban and made a complete recovery. Our patient case adds to the emerging literature suggesting that DOAC therapy is safe and efficacious for management of proven HIT