Patients with hypopigmented mycosis fungoides (HMF) present at a younger age than those with classic MF. Our goal was to describe the clinical presentation, histopathologic features and long-term outcome in patients who developed HMF before the age of 21. It was observed that among 69 pediatric patients diagnosed with MF between 1992 and 2010, 50 had HMF. Thirty-five patients had clinical follow-up. There were 37 males and 32 females with a mean age of 13.6 years. Most patients were African American or Hispanic and presented with multiple hypopigmented patches. All biopsies showed epidermotropism of T-lymphocytes, whereas fibroplasia and lichenoid infiltrate were variable. All specimens tested were CD8+. Treatment modalities included topical steroids, narrow band ultraviolet B and psoralen and ultraviolet A. HMF patients were followed for <1-12 years. Most children responded to treatment, but recurrence rates were high. One patient progressed to plaque/tumor stage. Others did not progress; however, many were lost to follow-up. We present a large cohort of children with HMF and report on the features of disease and progression. A major difference in histology of HMF was lack of fibroplasia and lichenoid infiltrate, probably because of presentation in the early patch stage. Most patients have a waxing-and-waning course and relapse after discontinuation of therapy, requiring repetitive treatment.
Class III β-tubulin (βIII-tubulin) has been associated with tumor response to taxane-based therapies in breast cancer. However its role in the neoadjuvant setting has not been explored. We evaluated βIII-tubulin expression by immunohistochemistry in 44 patients, and found high expression associated with good pathologic response in estrogen receptor–negative (ER−) breast cancers. Our results give strong reason to consider βIII-tubulin as a predictive biomarker for neoadjuvant chemotherapy response. Background Expression of class III β–tubulin (βIII-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies including breast cancer. However its predictive value in a neoadjuvant setting in breast cancer remains unexplored. The objective of this explorative study was to determine whether βIII-tubulin expression in breast cancer correlated with pathologic characteristics and whether its expression was predictive of response to neoadjuvant chemotherapy. Patients and Methods We determined βIII-tubulin expression in 85 breast cancers, including 41 localized breast cancers treated with primary surgery and 44 treated with neoadjuvant chemotherapy before surgery. βIII-tubulin expression was evaluated by immunohistochemical methods and was correlated with pathologic characteristics and response to neoadjuvant chemotherapy using residual cancer burden (RCB) score. Results High βIII-tubulin expression was significantly associated with poorly differentiated high-grade breast cancers (P = .003) but not with tumor size, estrogen receptor (ER) status, or human epidermal growth factor receptor 2 (HER2)/neu overexpression. In ER− tumors treated with neoadjuvant chemotherapy, high βIII-tubulin expression was associated with a significantly greater likelihood of achieving a good pathologic response to chemotherapy as reflected by lower RCB scores (P = .021). Conclusion This study reveals differential βIII-tubulin expression in breast cancers of different histologic grades, hormone receptors, and HER2/neu status. It also suggests a potential role for βIII-tubulin as a predictive biomarker for response in neoadjuvant chemotherapy for ER− breast cancer, which has not been previously reported. These data provide a strong rationale for considering βIII-tubulin status and further validation of this marker in a large study.
b b-thalassemias are characterized by an imbalance of globin chains with an excess of a-chains which precipitates in erythroid precursors and red blood cells (RBCs) leading to inefficient erythropoiesis. The severity of the disease correlates with the amount of unpaired achains. Our goal was to develop a simple test for evaluation of the free a-hemoglobin pool present in RBC lysates. Alpha-Hemoglobin Stabilizing Protein (AHSP), the chaperone of a-Hb, was used to trap excess aHb. A recombinant GST-AHSP fusion protein was bound to an affinity micro-column and then incubated with hemolysates of patients. After washing, the a-Hb was quantified by spectrophotometry in the elution fraction. This assay was applied to 54 patients: 28 without apparent Hb disorder, 20 b-thalassemic and 6 a-thalassemic. The average value of free a-Hb pool was 93 ± 21 ppm (ng of free a-Hb per mg of Hb subunits) in patients without Hb disorder, while it varies from 119 to 1,756 ppm, in b-thalassemic patients and correlated with genotype. In contrast, the value of the free a-Hb pool was decreased in a-thalassemic patients (65 ± 26 ppm). This assay may help to characterize b-thalassemia phenotypes and to follow the evolution of the globin chain imbalance (a/b+c ratio) in response to treatment.b-thalassemias (b-thal) are inherited autosomal diseases characterized by a decreased or abolished b-globin chain biosynthesis [1]. During the transition of g to b globin expression in the first year of life, the clinical severity is mainly related to the ratio a/b1g which indicates the level of chain disequilibrium. b-thal are generally classified as minor, intermediate, or major phenotype, and encompass a wide clinical spectrum ranging from asymptomatic carriers to forms that can be lethal in the absence of extensive treatment. Different factors can modulate the severity of this disease [2] such as the magnitude of the decrease of the b globin synthesis, for example hemoglobin E (Hb E b26Glu?Lys) [3], or with the co-inheritance of (i) an a-thalassemia (a-thal) [4], (ii) a triplicated a-globin gene [5] or (iii) a low but variable residual capacity of g globin production which can have the phenotype of a hereditary persistence of fetal Hb (Hb F a 2 g 2 ) [6].The imbalance between a and non a-globin (g1d1b) synthesis was established by radioactive in vitro biosynthesis of globin chains from reticulocytes or of bone marrow of b-thalassemic patients [7][8][9][10]. This imbalance leads to an excess of highly unstable free a-hemoglobin (a-Hb), precipitating on the cell membrane and acting as active oxidants causing apoptosis and inefficient erythropoiesis [1,11]. The severity of b-thal is directly correlated with the degree of imbalance as quantified by the amount of unbound a-globin chain [12]. Many studies have shown that one observes a soluble a chain fraction present in the cytosolic RBC and an insoluble a chain fraction in the membrane of b-thalassemic erythrocytes [13,14]. Because of technical difficulties and the burden of using radioactive materials, ...
Background In spite of profound reduction in incidence, cervical cancer claims >275,000 lives annually. Previously we demonstrated efficacy and safety of radioimmunotherapy directed at HPV16 E6 oncoprotein in experimental cervical cancer. Materials & methods We undertook a direct comparison of targeting E7 and E6 oncoproteins with specific 188Rhenium-labeled monoclonal antibodies in CasKi subcutaneous xenografts of cervical cancer cells in mice. Results The most significant tumor inhibition was seen in radioimmunotherapy-treated mice, followed by the unlabeled monoclonal antibodies to E6 and E7. No hematological toxicity was observed. Immunohistochemistry suggests that the effect of unlabeled antibodies is C3 complement mediated. Conclusion We have demonstrated for the first time that radioimmunotherapy directed toward E7 oncoprotein inhibits experimental tumors growth, decreases E7 expression and may offer a novel approach to cervical cancer therapy.
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