Prostate cancer is the second most prevalent malignancy worldwide. In the early stages, the development of prostate cancer is dependent on androgens. Over time with androgen deprivation therapy, 20% ...of prostate cancers progress to a castration-resistant form. Novel treatments for prostate cancers are still urgently needed. Erianin is a plant-derived bibenzyl compound. We report herein that erianin exhibits anti-tumor effects in androgen-sensitive and castration-resistant prostate cancer cells through different mechanisms. Erianin induces endoplasmic reticulum stress-associated apoptosis in androgen-sensitive prostate cancer cells. It also triggers pro-survival autophagic responses, as inhibition of autophagy predisposes to apoptosis. In contrast, erianin fails to induce apoptosis in castration-resistant prostate cancer cells. Instead, it results in cell cycle arrest at the M phase. Mechanistically, C16 ceramide dictates differential responses of androgen-sensitive and castration-resistant prostate cancer cells to erianin. Erianin elevates C16 ceramide level in androgen-sensitive but not castration-resistant prostate cancer cells. Overexpression of ceramide synthase 5 that specifically produces C16 ceramide enables erianin to induce apoptosis in castration-resistant prostate cancer cells. Our study provides both experimental evidence and mechanistic data showing that erianin is a potential treatment option for prostate cancers.
Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have ...been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.
Abstract Background Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic ...disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study is to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC. Study Design Patients who underwent curative-intent repeat resection for recurrent ACC at one of thirteen academic medical centers, participating in the United States ACC Study Group, were identified. Endpoints included morbidity, mortality, and overall survival. Results Fifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997-2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%) and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease free interval (DFI) <12 months, and extrapulmonary distant metastases were independent predictors of poor survival. A clinical score consisting of 1-point each for the above three variables demonstrated good discrimination in predicting survival after repeat resection (5-year: 72% for 0-points, 32% for 1 point, 0 % for 2 or 3 points, p=0.0006, AUC=0.78). Conclusions Long-term survival after repeat resection for recurrent adrenocortical carcinoma is feasible when two of the following factors are present: solitary tumor, DFI >12months, and locoregional or pulmonary recurrence.
Patient Perceptions in Mast Cell Disorders Jennings, Susan V.; Slee, Valerie M.; Zack, Rachel M. ...
Immunology and allergy clinics of North America,
08/2018, Letnik:
38, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Understanding experiences, perceptions, and perspectives of patients with a mast cell disorder (MCD), including cutaneous mastocytosis, systemic mastocytosis, mast cell activation syndromes, and ...hereditary α-tryptasemia, is an important aspect of successful care, treatment, and informed development of novel therapies. This article reviews existing studies and presents new data on MCD patient perceptions regarding medical care, symptoms, allergies/sensitivities, triggers, future health/disease progression, treatment, impact on daily living, quality of life, support needs, and concerns regarding possible familial disease. Discussion includes aspects affecting the MCD community that require further consideration and development.
Mast cells (MC) are specialized immune cells that play a key role in anaphylactic reactions. Growth, differentiation, and function of these cells are regulated by a complex network of cytokines, ...surface receptors, signaling molecules, the microenvironment, and the genetic background. A number of previous and more recent data suggest that MC are heterogeneous in terms of cytokine-regulation, expression of cytoplasmic and cell surface antigens, and response to ligands. MC heterogeneity is often organ-specific and is considered to be related to MC plasticity, disease-associated factors, and the maturation stage of the cells. The stem cell factor (SCF) receptor KIT (CD117) is expressed on all types of MC independent of maturation and activation-status. In systemic mastocytosis (SM), KIT is often expressed in MC in a mutated and constitutively activated form. In these patients, MC aberrantly display CD2 and CD25, diagnostic markers of neoplastic MC in all SM variants. In advanced SM, MC co-express substantial amounts of CD30, whereas CD2 expression on MC may be decreased compared to indolent SM. Other surface molecules, such as CD63 or CD203c, are overexpressed on neoplastic MC in SM, and are further upregulated upon cross-linking of the IgE receptor. Some of the cell surface antigens expressed on MC or their progenitors may serve as therapeutic targets in the future. These targets include CD25, CD30, CD33, CD44, and CD117/KIT. The current article provides an overview on cell surface antigens and target receptors expressed by MC in physiologic and reactive tissues, and in patients with SM, with special reference to phenotypic heterogeneity and clinical implications.
Summary Reactive bone marrow mast cells reliably lack the morphologic, immunophenotypic, and molecular features of systemic mastocytosis (SM). We report two unusual cases of acquired aplastic anemia ...(AA) in which multifocal aggregates of bone marrow mast cells fulfilled morphologic and immunophenotypic criteria for SM according to the World Health Organization 2008 classification. In the absence of clinical symptoms attributable to SM, the patients were treated with immunosuppressive therapy directed towards AA. Clinical follow-up and subsequent bone marrow examination revealed no evidence of overt SM in either patient. These cases represent, to our knowledge, the first reported instances in which criteria for SM have been fulfilled in the presence of AA. However, given the clinical courses followed by our patients, the incidental identification of mast cell lesions consistent with indolent SM may be of uncertain significance in the setting of AA.
Systemic mastocytosis George, Tracy I; Horny, Hans-Peter
Hematology/oncology clinics of North America,
10/2011, Letnik:
25, Številka:
5
Journal Article
Recenzirano
An unusual disease, mastocytosis challenges the pathologist with a variety of morphologic appearances and heterogeneous clinical presentations ranging from skin manifestations (pruritus, urticaria, ...dermatographism) to systemic signs and symptoms indicative of mast cell mediator release, including flushing, hypotension, headache, and anaphylaxis among others. In this article, we focus on recognizing the cytology, histopathology, clinical features, and prognostic implications of systemic mastocytosis, a clonal and neoplastic mast cell proliferation infiltrating extracutaneous organ(s) with or without skin involvement. Diagnostic pitfalls are reviewed with ancillary studies to help unmask the mast cell and exclude morphologic mimics.
Venous thromboembolism accounts for approximately 9% of pregnancy-related deaths in the United States. National guidelines recommend postpartum risk stratification and pharmacologic prophylaxis in ...at-risk individuals. Knowledge on modern rates of postpartum pharmacologic thromboprophylaxis and its associated risks is limited.
This study aimed to describe the rate of, and factors associated with, initiation of postpartum pharmacologic prophylaxis for venous thromboembolism, and to assess associated adverse outcomes.
This was a secondary analysis of a multicenter cohort of individuals delivering on randomly selected days at 17 US hospitals (2019–2020). Medical records were reviewed by trained and certified personnel. Those with an antepartum diagnosis of venous thromboembolism, receiving antepartum anticoagulation, or known SARS-CoV-2 infection were excluded. The primary outcome was use of postpartum pharmacologic thromboprophylaxis. Secondary outcomes included bleeding complications, surgical site infection, hospital readmission, and venous thromboembolism through 6 weeks postpartum. The rate of thromboprophylaxis administration was assessed by mode of delivery, institution, and continuance to the outpatient setting. Multivariable regression models were developed using k-fold cross-validation with stepwise backward elimination to evaluate factors associated with thromboprophylaxis administration. Univariable and multivariable logistic models with propensity score covariate adjustment were performed to assess the association between thromboprophylaxis administration and adverse outcomes.
Of 21,114 individuals in the analytical cohort, 11.9% (95% confidence interval, 11.4%–12.3%) received postpartum pharmacologic thromboprophylaxis; the frequency of receipt was 29.8% (95% confidence interval, 28.7%–30.9%) following cesarean and 3.5% (95% confidence interval, 3.2%–3.8%) following vaginal delivery. Institutional rates of prophylaxis varied from 0.21% to 34.8%. Most individuals (83.3%) received thromboprophylaxis only as inpatients. In adjusted analysis, cesarean delivery (adjusted odds ratio, 19.17; 95% confidence interval, 16.70–22.00), hysterectomy (adjusted odds ratio, 15.70; 95% confidence interval, 4.35–56.65), and obesity (adjusted odds ratio, 3.45; 95% confidence interval, 3.02–3.95) were the strongest factors associated with thromboprophylaxis administration. Thromboprophylaxis administration was not associated with surgical site infection (0.9% vs 0.6%; odds ratio, 1.48; 95% confidence interval, 0.80–2.74), bleeding complications (0.2% vs 0.1%; odds ratio, 2.60; 95% confidence interval, 0.99–6.80), or postpartum readmission (0.9% vs 0.3%; adjusted odds ratio, 1.38; 95% confidence interval, 0.68–2.81). The overall rate of venous thromboembolism was 0.06% (95% confidence interval, 0.03%–0.10%) and was higher in those receiving prophylaxis (0.2%) compared with those not receiving prophylaxis (0.04%).
Approximately 1 in 10 patients received postpartum pharmacologic thromboprophylaxis in this US cohort. Rates of prophylaxis varied widely by institution. Cesarean delivery, hysterectomy, and obesity were predominant factors associated with postpartum thromboprophylaxis administration.
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