Chemotherapy-related neuropathic symptoms and functional impairment in adult survivors of extracranial solid tumors of childhood: results from the St. Jude Lifetime Cohort Study.

OBJECTIVES: To ascertain prevalence of peripheral sensory and motor neuropathy, and to evaluate impairments in relation to function. DESIGN: St. Jude Lifetime Cohort Study, a clinical follow-up study designed to evaluate adverse late effects in adult survivors of childhood cancer. SETTING: A children's research hospital. PARTICIPANTS: Eligibility required treatment for an extracranial solid malignancy between 1962 and 2002, age ≥ 18 years, ≥ 10 years postdiagnosis, and no history of cranial radiation. Survivors (N=531) were included in the evaluation with a median age of 32 years and a median time from diagnosis of 25 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary exposure measures were cumulative doses of vinca-alkaloid and platinum-based chemotherapies. Survivors with scores ≥ 1 on the sensory subscale of the Modified Total Neuropathy Score were classified with prevalent sensory impairment. Those with sex-specific z scores of ≤-1.3 for dorsiflexion strength were classified with prevalent motor impairment. Participants completed the 6-minute walk test (endurance), the Timed Up & Go test (mobility), and the Sensory Organization Test (balance). RESULTS: The prevalence of sensory and motor impairment was 20% and 17.5%, respectively. Vinca-alkaloid exposure was associated with an increased risk of motor impairment (adjusted odds ratio [OR]=1.66; 95% confidence interval [CI], 1.04-2.64) without evidence for a dose response. Platinum exposure was associated with increased risk of sensory impairment (adjusted OR=1.62; 95% CI, .97-2.72) without evidence of a dose response. Sensory impairment was associated with poor endurance (OR=1.99; 95% CI, .99-4.0) and mobility (OR=1.65; 95% CI, .96-2.83). CONCLUSIONS: Vincristine and cisplatin exposure may increase risk for long-term motor and sensory impairment, respectively. Survivors with sensory impairment are at increased risk for functional performance limitations.

Genetics of metallothioneins in Drosophilamelanogaster.

Metallothioneins (MTs) are ubiquitous metal-chelating proteins involved in cellular metal homeostasis. MTs were found to be related with almost all the biological processes and their malfunctioning is responsible for a lot of important human diseases. Invertebrate MTs were also used broadly as biomarkers of metal contamination due to their inducible expression by metal exposure. MT system plays a significant role in maintaining human health and ecological stability. Drosophila melanogaster, the vinegar fly, is a perfect model for studying insect MT systems. Six MTs were identified in D. melanogaster, and were designated MtnA to F. All the MTs are considered as Cu-thioneins except for MtnF, which is putatively a Zn-thionein. Expression of all the MTs are regulated by MTF-1/MRE system, thus being able to be induced by heavy metal exposure. The expression pattern and function of separated MTs are partially overlapped and partially distinct. In this work, we made a summary of all the studies on D. melanogaster MTs. From this review, we noted that, compared with studies on mammalian MTs, the understanding of the MT system of D. melanogaster and other invertebrates, especially the regulation mechanism for MT expression and protein-protein interaction with them, is still in a low level.

Value of Contrast-Enhanced Ultrasound in Mummified Thyroid Nodules.

Mummified thyroid nodules (MTNs) are rarely reported and are usually misdiagnosed as malignant nodules. This article first reviewed the contrast-enhanced ultrasound (CEUS) enhancement features of 218 MTNs and classified them into three (A, B, C) patterns. The A pattern MTNs show linear hypo-enhancement, the B pattern MTNs show heterogeneous hypo-enhancement, and the C pattern MTNs show no enhancement in thyroid nodules. The A and C pattern enhancements of MTNs demonstrated a high specificity compared with the enhancement of previously reported typical papillary thyroid carcinomas (PTCs). To further study the B pattern MTNs, 24 B pattern MTNs and 42 PTCs were enrolled in this study, and CEUS parameters for each nodule were evaluated. Univariate analysis indicated that compared with PTCs, the B pattern MTNs more frequently exhibited heterogeneous hypo-enhancement and clear margins after clearance (p <0.05). A multivariate analysis revealed that heterogeneous hypo-enhancement and clear margins after clearance were independent characteristics related to the B pattern MTNs for differentiating them from PTCs (p <0.05). Thus, preoperative CEUS may provide more important information for distinguishing MTNs from malignant thyroid nodules to avoid surgical excisions or unnecessary fine-needle aspiration (FNA).

Anti-CD19 mAb modified mesoporous titanium dioxide as exclusively targeting vector for efficient B-lymphoblastic leukemia therapy.

B lymphoblastic leukemia (B-LL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mainly occurs in children and adolescents and is one of the main causes of death from malignant tumors in this population. The surface marker CD19 is specifically expressed on the membrane of most malignant B-cells, which is widely used as a marker of B-LL antigen-specific immunotherapy. In this study, mesoporous titanium dioxide nanoparticles (MTNs)-based antibody drug delivery system was designed for B-LL treatment. Anti-CD19 monoclonal antibody was conjugated to PEGylated MTNs, and doxorubicin (DOX) was loaded in the nanoparticle. The CD19-PEG-MTN/DOX nanoparticle could recognize CD19+B-LL cell lines and induced them apoptosis, but nontoxic for the normal cells. Further, after treated with CD19-PEG-MTN/DOX nanoparticle, pro-apoptotic proteins Bax and Caspase-3 in KOPN 8 and NALM-6 cells were significantly upregulated, but anti-apoptotic proteins Bcl2, MCL-1, HSP 70, and BAG 3 were downregulated, which indicated the activation of the apoptosis pathway by the nanodrug. By contrast, CD19-PEG-MTN/DOX didn't play a part on CD19-cell line U937. Besides, the cytotoxicity of CD19-PEG-MTN/DOX was low with good biocompatibility. Collectively, CD19-PEG-MTN/DOX is a promising antitumor nanodrug for the treatment of B-LL.