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The sarcomatoid variant of anaplastic large cell lymphoma is an extremely rare histologic pattern of anaplastic large cell lymphoma that consists of spindle-shaped neoplastic cells and is easily misdiagnosed as a soft tissue sarcoma. We report a case of the sarcomatoid variant of anaplastic large cell lymphoma that was initially diagnosed as an inflammatory myofibroblastic tumor in our hospital and as liposarcoma after consultation. This article analyzed the features of this entity by reviewing the literature. Only 15 cases have been reported, most of which were misdiagnosed as sarcoma, sarcomatoid carcinoma, or inflammatory myofibroblastic tumor. Most of the reported cases showed a myxoid stroma, with a variable number of inflammatory cells. The hallmark cells usually can be found by careful evaluation of the slides. Immunohistochemistry including CD30, EMA, and ALK are the most useful for diagnosis. Most are III or IV stage, and have a good prognosis after chemotherapy.Insulinoma-associated protein-1 (INSM1), a transcription factor encoded by the insulinoma associated-1 gene, is a second-generation biomarker of neuroendocrine differentiation. Its sensitivity and specificity in comparison with chromogranin-A and synaptophysin have been extensively validated in several organs, but evidence regarding its expression in mammary neoplasms is limited. In this study, INSM1 immunohistochemistry was validated in a cohort of 22 mammary neoplasms, enriched with special type breast carcinomas with known neuroendocrine differentiation as determined by immunohistochemistry for synaptophysin and chromogranin-A. Subsequently, INSM1 expression was evaluated in a consecutive series of 66 invasive breast cancer biopsies. In the validation cohort, 14 tumors were synaptophysin-positive, of which all but one showed INSM1 immunoreactivity. Eight tumors were synaptophysin-negative, of which 3 showed focal nuclear INSM1 expression. Six tumors were chromogranin-A-positive, of which one was INSM1-negative. When compared with synaptophysin, INSM1 seems more sensitive but less specific than chromogranin-A. In the biopsy cohort, only one invasive carcinoma of no special type showed substantial INSM1 immunoreactivity (ie, 25% of the tumor cells). Three more cases showed 1% nuclear INSM1 staining. We conclude that neuroendocrine differentiation in invasive breast carcinoma of no special type is a rare finding. Immunohistochemical biomarkers, comprising INSM1 as well as the first-generation biomarkers chromogranin-A and synaptophysin, are useful to distinguish neuroendocrine differentiation in breast neoplasms. The identification of neuroendocrine differentiation can be helpful to establish the diagnosis of special type breast carcinomas such as solid papillary carcinoma.

Toxicity from off-target heating with magnetic hyperthermia (MHT) is generally assumed to be understood. MHT research focuses on development of more potent heating magnetic iron oxide nanoparticles (MIONs), yet our understanding of factors that define biodistribution following systemic delivery remains limited. Preclinical development relies on mouse models, thus understanding off-target heating with MHT in mice provides critical knowledge for clinical development.

Eight-week old female nude mice received a single tail vein injection of bionized nanoferrite (BNF) MIONs or a counterpart labeled with a polyclonal human antibody (BNF-IgG) at 1 mg, 3 mg or 5 mg Fe/mouse on day 1. On day 3, mice were exposed to an alternating magnetic field (AMF) having amplitude of 32, 48 or 64 kA/m at ∼145 kHz for 20 min. Twenty-four hours later, blood, livers and spleens were harvested and analyzed.

Damage to livers was apparent by histology and serum liver enzymes following MHT with BNF or BNF-IgG at doses ≥3 mg Fe and AMF amplitudes ≥48 kA/m. Differences between effects with BNF vs. BNF-IgG at a dose of 3 mg Fe were noted in all measures, with less damage and increased survival occurring in mice injected with BNF-IgG. Necropsies revealed severe damage to duodenum and upper small intestines, likely the immediate cause of death at the highest MHT doses.

Results demonstrate that the MION coating affects biodistribution, which in turn determines off-target effects. Developments to improve heating capabilities of MIONs may be clinically irrelevant without better control of biodistribution.

Results demonstrate that the MION coating affects biodistribution, which in turn determines off-target effects. Developments to improve heating capabilities of MIONs may be clinically irrelevant without better control of biodistribution.

This clinical study was developed to primarily evaluate the Complete Cytopathological Response Rate of Cervical Intraepithelial Neoplasms to PDT using chitosan nanocapsules containing Chlorocyan-aluminum phthalocyanine as a photoactive agent. Analyses of the Free Recurrence Interval, toxicity profile (immediate and late), and complications (immediate and late), were secondarily analyzed.

This study was previously approved by the National Council of Ethics in Research of Brazil (CONEP), on May 28, 2014, under case number 19182113.4.0000.5009. On the surface of the cervix of each selected patient was applied one mL of the formulated gel, and after 30 min, the light was applied. Reports or the identification of adverse effects and/or complications were observed in follow-up visits, in addition to the collection of cervical oncotic cytology.

Out of the total group, 11 (91.7%) primarily treated patients evolved with negative cervical oncotic cytology as soon as in the first evaluation following treatment, and one did not achieve any therapeutic benefit, even after reapplication. Two patients with initially positive response presented cytological recurrence determined by histopathology. A new round of PDT was developed, and both evolved with cytological remission three weeks later, remaining negative until the last follow-up. No important side effects were observed in all the patients.

Our trial demonstrates that treatment of CIN 1 and 2 lesions using our PDT formulation is feasible and safe. Large randomized clinical trials are required to establish efficacy.

Our trial demonstrates that treatment of CIN 1 and 2 lesions using our PDT formulation is feasible and safe. Large randomized clinical trials are required to establish efficacy.Immunotherapy to treat cancer is now an established clinical approach. Immunotherapy can be applied systemically, as done with checkpoint blockade antibodies, but it can also be injected directly into identified tumors, in a strategy of in situ vaccination (ISV). ISV is designed to stimulate a strong local antitumor immune response involving both innate and adaptive immune cells, and through this generate a systemic antitumor immune response against metastatic tumors. A variety of ISVs have been utilized to generate an immunostimulatory tumor microenvironment (TME). These include attenuated microorganisms, recombinant proteins, small molecules, physical disruptors of TME (alternating magnetic and focused ultrasound heating, photothermal therapy, and radiotherapy), and more recently nanoparticles (NPs). NPs are attractive and unique since they can load multiple drugs or other reagents to influence immune and cancer cell functions in the TME, affording a unique opportunity to stimulate antitumor immunity. Here, we describe the NP-ISV therapeutic mechanisms, review chemically synthesized NPs (i.e., liposomes, polymeric, chitosan-based, inorganic NPs, etc.), biologically derived NPs (virus and bacteria-based NPs), and energy-activated NP-ISVs in the context of their use as local ISV. Data suggests that NP-ISVs can enhance outcomes of immunotherapeutic regimens including those utilizing tumor hyperthermia and checkpoint blockade therapies.Magnetic fluid hyperthermia (MFH) has been widely investigated as a treatment tool for cancer and other diseases. However, focusing traditional MFH to a tumor deep in the body is not feasible because the in vivo wavelength of 300 kHz very low frequency (VLF) excitation fields is longer than 100 m. Recently we demonstrated that millimeter-precision localized heating can be achieved by combining magnetic particle imaging (MPI) with MFH. In principle, real-time MPI imaging can also guide the location and dosing of MFH treatments. selleck Hence, the combination of MPI imaging plus real time localized MPI-MFH could soon permit closed-loop high-resolution hyperthermia treatment. In this review, we will discuss the fundamentals of localized MFH (e.g. physics and biosafety limitations), hardware implementation, MPI real-time guidance, and new research directions on MPI-MFH. We will also discuss how the scale up to human-sized MPI-MFH scanners could proceed.Convective transport is an important phenomenon for nanomedicine delivery. We present an imaging-based approach to recover tissue properties that are significant in the accumulation of nanoparticles delivered via systemic methods. The classical pharmacokinetic analysis develops governing equations for the particle transport from a first principle mass balance. Fundamentally, the governing equations for compartmental mass balance represent a spatially invariant mass transport between compartments and do not capture spatially variant convection phenomena. Further, the parameters recovered from this approach do not necessarily have direct meaning with respect to the governing equations for convective transport. In our approach, a framework is presented for directly measuring permeability in the sense of Darcy flow through porous tissue. Measurements from our approach are compared to an extended Tofts model as a control. We demonstrate that a pixel-wise iterative clustering algorithm may be applied to reduce the parameter space of the measurements. We show that measurements obtained from our approach are correlated with measurements obtained from the extended Tofts model control. These correlations demonstrate that the proposed approach contains similar information to an established compartmental model and may be useful in providing an alternative theoretical framework for parameterizing mathematical models for treatment planning and diagnostic studies involving nanomedicine where convection dominated effects are important.Immune checkpoint blockade (ICB) comprising monoclonal antibodies (mAbs) against immune ‘checkpoints’, such as CTLA-4 and the PD1/PDL1 axis have dramatically improved clinical outcomes for patients with cancer. However, ICB by itself has failed to provide benefit in a wide range of solid tumors, where recurrence still occurs with high incidence. These poor response rates may be due to the therapeutic shortcomings of ICB; namely, a lack of cancer-specific cytotoxicity and ability to debulk tumors. To overcome these limitations, effective ICB therapy may require the combination with other complementary therapeutic platforms. Here, we propose that photothermal therapy (PTT) is an ideal therapeutic modality for combination with ICB because it can generate both tumor-specific cytotoxicity and immunogenicity. PTT elicits these specific effects because it is a localized thermal ablation technique that utilizes light-responsive nanoparticles activated by a wavelength-matched laser. While ICB immunotherapy alone improves cancer immunogenicity but does not generate robust antitumor cytotoxicity, nanoparticle-based PTT elicits targeted and controlled cytotoxicity but sub-optimal long-term immunogenicity.