To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC).

To investigate imaging findings in patients with primary breast sarcoma (PBS).

Cutaneous T cell lymphomas (CTCLs) are heterogeneous, with a prognosis determined in large part by combined clinical, histopathologic, and immunophenotypic features. They are classified under the WHO-EORTC classification of primary cutaneous lymphoma. Whether or not a patient diagnosed with CTCL will experience an aggressive course may not be completely predictable; however, certain subtypes have been proven to be associated with a poor response to therapy and/or short survival. These aggressive subtypes may be diagnosed by certain histologic, immunophenotypic, and clinical features; however, there are benign lymphoproliferative disorders (LPD), such as lymphomatoid papulosis (LyP) that present with biopsy findings that simulate an aggressive lymphoma. Moreover, some of the well-recognized aggressive lymphomas may rarely follow an indolent course, while otherwise indolent lymphomas may act aggressively. This review will focus on the non-mycosis fungoides (MF) aggressive subtypes, as well as potentially aggressive presentations of MF.

Tumors arising from or secondarily involving the vena cava (VC) are broad-spectrum diseases, ranging from benign to malignant. The benign tumors include myxoma, leiomyomatosis and leiomyoma. The primary malignant tumors of the VC are rare, and of these rare entities, leiomyosarcoma is the most frequently encountered. The direct extension of a tumor arising from an adjacent organ such as hepatocellular carcinoma or renal cell carcinoma is more common than primary malignant tumor in the inferior VC. In this article, the authors review the spectrum of VC pathologic processes and the relevant findings from magnetic resonance imaging, ultrasonography, and computed tomography.

In the study of complex diseases using genome-wide expression data from clinical samples, a difficult case is the identification and mapping of the gene signatures associated to the stages that occur in the progression of a disease. The stages usually correspond to different subtypes or classes of the disease, and the difficulty to identify them often comes from patient heterogeneity and sample variability that can hide the biomedical relevant changes that characterize each stage, making standard differential analysis inadequate or inefficient.

Synthesis of carbon dots (Cdots) via chemical route involves disintegration of carbon materials into nano-domains, wherein, after extraction of Cdots, the remaining carbon material is discarded. The present work focuses on studying even the leftover carbon residue namely, carbon nanobeads (CNBs) as an equally important material for applications on par with that of carbon dot. It employs oxidative treatment of carbonised gum olibanum resin (GOR) to produce the carbons namely Cdots and CNBs (as the residue). The Cdots (~5-10nm) exhibit blue-green fluorescence with an optical absorption at ~300nm unlike the CNBs (40-50nm) which fail to exhibit fluorescence. The fluorescence behaviour exhibited by Cdots were utilized for heavy metal ion sensing of Pb2+, Hg2+ and Cd2+ ions in aqueous media. Interestingly, both Cdots and CNBs are biocompatible to normal cell lines but cytotoxic to cancer cell lines, observed during several in vitro experiments (cell viability assay, cell cycle assay, apoptosis assay, ROS determination assay, caspase-9 activity assay). Additionally, Cdots exhibit bright green fluorescence in B16F10 cells. The Cdots and CNB's demonstrate multifunctional activities (sensor, cellular imaging and cancer therapy) in biomedical applications.

Betulinic acid (BA), a pentacyclic lupine-type triterpene, is reported to inhibit cell growth in a variety of cancers. However, its efficacy is limited by its poor aqueous solubility and relatively short half-life. In this study, BA-monomethoxy polyethylene glycol (mPEG) conjugate was synthesized by covalent coupling the C-28 carboxylic acid position of BA with amine groups of mPEG, in order to improve its solubility and anticancer efficacy. mPEG-BA conjugate was characterized using various analytical techniques including NMR, FT-IR and MALDI-MS. The mPEG-BA conjugate was cytotoxic, demonstrated internalization and induced cell apoptosis in Hep3B and Huh7 hepatic cancer cells. The western-blot analysis revealed, marked decrease in Bcl-2/Bax ratio, and increase in cleaved-PARP and cleaved-caspase-3 expressions. In vivo studies in Ehrlich ascites tumor (EAT) model following intravenous administration demonstrated significant reduction in tumor volume in case of PEGylated BA as compare to native BA. Furthermore, PEGylated BA treated EAT mice showed no biochemical and histological toxicities. These findings demonstrate the potential of PEGylated BA in cancer therapy, with improved water solubility and efficacy.

Renal cell carcinoma has a tendency for vascular invasion and may extend into the inferior vena cava and even into the right-sided cardiac chambers. It has been reported that nephrectomy with thrombectomy can provide immediate palliation of symptoms with 5-year survival rates of up to 72% in the absence of nodal or distant metastasis. The location of the tumor dictates the anesthetic and surgical approach, as extension into the heart often necessitates cardiac surgical involvement. Renal cell carcinoma with vena cava tumor thrombus extending into the right cardiac chamber usually requires cardiopulmonary bypass and occasionally deep hypothermic circulatory arrest for surgical resection, and anesthetic approach should be tailored to each individual case. Thorough preoperative evaluation and the commitment of a multidisciplinary surgery team are indispensable.

Patients undergoing free tissue reconstruction are at risk for development of an anastomotic pseudoaneurysm, which may present as delayed neck hemorrhage or a pulsatile neck mass. Diagnosis may be achieved by noninvasive imaging, angiography, and exploration. Management strategies for head and neck pseudoaneurysms have included open vessel ligation, open direct vessel repair, endovascular parent vessel embolization, and, most recently, endovascular pseudoaneurysm embolization. In patients with anastomotic pseudoaneurysms where adequate flap inosculation is doubted, endovascular pseudoaneurysm embolization with pedicle preservation may be an appropriate primary treatment approach. We discuss the successful endovascular coiling of an external carotid artery branch anastomotic pseudoaneurysm in a patient one month after free tissue reconstruction of a total laryngopharyngectomy and partial glossectomy defect.

Although chondrosarcoma is a common malignant bone tumor, cases arising in the rib are relatively rare. We experienced a case of chondrosarcoma arising in the right 10th rib during follow-up after lung cancer surgery. Although the finding of an osteolytic mass suggested a metastatic bone tumor, 18F-fluorodeoxyglucose positron-emission tomography demonstrated low fluorodeoxyglucose uptake, and a primary bone tumor was suspected. The bone tumor was resected and diagnosed as chondrosarcoma. Four years after resection, there has been no recurrence or metastasis. Positron-emission tomography was useful for differential diagnosis between a chondrosarcoma and a metastatic bone tumor.

A 23-year-old woman was referred to our center with hirsutism, acne, weight gain, weakness, and irregular menses. Laboratory tests revealed increased levels of cortisol and sex hormones, and reduced adrenocorticotropic hormone levels. The patient underwent a right adrenalectomy. Pathology of the resected right adrenal gland showed an adrenal carcinoma. Computed tomography 8 months after the surgery revealed a thymic mass that was not detected preoperatively. The frequency of rebound thymic hyperplasia after normalization of hypercortisolism is not known, but possibly as high as 40%. Physicians must be aware of this phenomenon to avoid unnecessary thoracic surgery.

Currently, primary hyperparathyroidism is the third most common endocrine disorder worldwide. In the last years, though, the numbers of patients with this diagnosis have been clearly increasing. Females are affected more often, and the age of patients is usually over 50 years. The diagnosis is guided by clinical symptoms of the patient and by biochemical and imaging methods results. [1] When parathyroid adenoma is identified as the source of primary hyperparathyroidism, the necessary extent of resection is performed. The present case involved a rapid diagnostic process necessary to stabilize the patient, together with localization of the adenoma for the indicated surgery. Ultrasound-guided exploration found a surprisingly large tumour of the parathyroid gland causing the acute clinical condition with symptoms suggestive of primary hyperparathyroidism with discrete mechanical compression of the upper mediastinum.Key words: critical diagnosis of hyperparathyroidism acute-active parathyroid adenoma extirpation of a huge parathyroid tumour - normalization of the clinical condition.

Safe and efficient drug delivery in a controllable fashion, especially remote and repeatable switch of on-demand drug release, is the subject of widespread attention. A kind of magnetic nanoparticles (DOX-Cit/CuS@Fe3O4-NPs) simultaneously consisted of Cit/CuS@Fe3O4 and doxorubicin (DOX) was presented. The drug release from DOX-Cit/CuS@Fe3O4-NPs could be successfully triggered by the presence of gelatinase, showing great promise for tumor-targeted drug release through an enzymatic degradation mechanism. Compared with free DOX, DOX-Cit/CuS@Fe3O4-NPs could not only specially deliver Cit/CuS@Fe3O4 and DOX into MCF-7 cells, but also could greatly improve the quantity of ROS produced in MCF-7 cells under of 980 nm laser irradiation. DOX-Cit/CuS@Fe3O4-NPs also had highly selective accumulation at tumor tissue of S180 tumor-bearing mice, which were along with a magnet near the tumor site. Furthermore, when combined with NIR laser irridation, DOX-Cit/CuS@Fe3O4-NPs showed a higher antitumor efficacy than the individual therapies in vitro and in vivo. This study showed that DOX-Cit/CuS@Fe3O4-NPs could be used as a platform for tumor chemotherapy, photothermal and photodynamic therapy.

Theranostic applications of gelatin nanospheres require two major components, a method of detection and good biocompatibility. We characterized the response of UTA-6 human osteosarcoma cells to the introduction of functionalized 90 bloom-based gelatin nanospheres (158 ± 49 nm) modified with three elements in different order: (a) hybridization with cadmium-based quantum dots for optical detection, (b) bioconjugation with anti-human IgG FAB (anti-IgG) for cell targeting, with/without (c) capping with polyethylene glycol on the surface for enhanced biocompatibility. A one-pot process is developed for incorporating quantum dots and antibody with gelatin nanospheres. Path A of modifying gelatin nanospheres with quantum dots first followed by anti-IgG resulted in a significantly greater cellular viability than Path B with anti-IgG first followed by quantum dots. Capping with polyethylene glycol as the final step in modification yielded significantly opposing results with decreases in Path A and increases in Path B. Three-dimensional z-stacking fluorescent images of hybrid gelatin nanospheres with anti-IgG is observed to have an increase in cellular association. The observed results suggest the modification order for building hybrid nanospheres may have an impact on cellular response.

We report a case of inflammatory myofibroblastic tumor of the posterior mediastinum and describe radiological features demonstrated on fluoro-esophagogram, computed tomography and positron-emission tomography. Fluoroscopic video-esophagogram was remarkable for an unusual polypoid lesion associated with partial esophageal obstruction and features of secondary achalasia. Computed tomography (CT) examination demonstrated coarse calcifications and air pockets, while unusual clinical features included an intraluminal esophageal lesion and local recurrence with endobronchial lesion.

Mouse F9 cells differentiate into primitive endoderm (PrE) following the activation of the canonical WNT-β-catenin pathway. The upregulation of Wnt6 and activation of β-catenin-TCF-LEF-dependent transcription is known to accompany differentiation, but the Frizzled (FZD) receptor responsible for transducing the WNT6 signal is not known. Eight of the 10 Fzd genes were found to be expressed in F9 cells, with Fzd7 being the most highly expressed, and chosen for further analysis. To alter steady-state Fzd7 levels and test the effect this has on differentiation, siRNA and overexpression approaches were used to knock-down and ectopically express the Fzd7 message, respectively. siRNA knock-down of Fzd7 resulted in reduced DAB2 levels, and the overexpression activated a TCF-LEF reporter, but neither approach affected differentiation. Our focus turned to how canonical WNT6 signaling was attenuated to allow PrE cells to form parietal endoderm (PE). Dkk1, encoding a WNT antagonist, was examined and results showed that its expression increased in F9 cells treated with retinoic acid (RA) or overexpressing Wnt6. F9 cells overexpressing human DKK1 or treated with DKK1-conditioned medium and then treated with RA failed to differentiate, indicating that a negative feedback loop involving WNT6 and DKK1 attenuates canonical WNT-β-catenin signaling, thereby allowing PE cells to differentiate.

PRPS1 (phosphoribosyl pyrophosphate synthetase 1), which drives the nucleotide biosynthesis pathway, modulates a variety of functions by providing central building blocks and cofactors for cell homeostasis. As tumor cells often display abnormal nucleotide metabolism, dysregulated de-novo nucleotide synthesis has potential impacts in cancers. We now report that PRPS1 is specifically and highly expressed in chemoresistant (CR) cancer cells derived from cisplatin-resistant human breast cancer cell lines SK-BR-3 and MCF-7. The inhibition of PRPS1 activity in CR cells by genetic silencing reduces cell viability and increases apoptosis in vitro, both of which can be further potentiated by cisplatin treatment. Significantly, such down-regulation of PRPS1 in CR cells when administered to nude mice enhanced the survival of those animals, as demonstrated by decreased tumor growth. Knockdown of PRPSI may cause these effects by potently inducing autonomous activation of caspase-3 and inhibiting the proliferation in the engrafted CR tumors. As a result, cisplatin sensitivity in a xenograft model of CR cancer cells can be restored by the down-regulation of PRPS1. Thus, PRPS1 inhibition may afford a therapeutic approach to relapsed patients with breast cancer, resistant to chemotherapy.

Pyrazoline is an important 5-membered nitrogen heterocycle that has been extensively researched. Ten derivatives were synthesized and tested for antileukemic effects on 2 human acute leukemia cell lines, K562 and Jurkat. The most cytotoxic of these derivatives, compound 21, was chosen for investigation of cytotoxicity mechanisms. The results obtained with selectivity calculations revealed that compound 21 is more selective for acute leukemia (K562 and Jurkat cell lines) than for other tumor cell lines. Moreover, compound 21 was not cytotoxic to normal cell lines, indicating a potential use in clinical tests. Compound 21 caused a significant cell cycle arrest in the S-phase in Jurkat cells and increased the proportion of cells in the sub G0/G1 phase in both cell lines. Cells treated with compound 21 demonstrated morphological changes characteristic of apoptosis in the EB/AO assay, confirmed by externalization of phosphatidylserine by the annexin V - fluorescein isothiocyanate method and by DNA fragmentation. An investigation of cytotoxicity mechanisms suggests the involvement of an intrinsic apoptosis pathway due to mitochondrial damage and an increase in the ratio of mitochondrial Bax/Bcl2. Pyrazoline 21 obeyed Lipinski's "rule of five" for drug-likeness. Based on these preliminary results, the antileukemic activity of compound 21 makes it a potential anticancer agent.

Ovarian epithelial tumors are the most common ovarian neoplasms, standing for more than half of all ovarian tumors. Borderline ovarian tumors represent a distinct group recognized by the World Health Organization (WHO), histologically distinct low ovarian carcinomas. They are tumors with low grade of malignancy with good progress and prognosis. The authors present a case of an ovarian tumor with diagnosis problems. It was the case of a 38-year-old patient with no genital pathological history, presenting hypogastric pain, dysmenorrhea, abdominal distension. The imaging performed examinations suggested an ovarian tumor with potential malignancy. The symptoms were nonspecific and the treatment was surgical. The piece was processed by paraffin inclusion and microscopically examined. Although the imaging examinations may be suggestive for potentially malignant lesions, the histopathological relation with the immunohistochemical one is the one that establishes the diagnosis. Following these examinations, there was established an ovarian borderline tumor. This is included in the lesions with low malignancy, the further evolution of the patient being a good one. The purpose of this presentation was the warning of the importance of histopathological examination linked with the immunohistochemical one, although the imaging may present lesions with malignancy criteria. Also, it was performed a literature review of borderline tumors in young women in terms of diagnosis and therapeutic conduct.