Isothermal titration calorimetry was used to probe how salts influence the thermodynamics of binding of guests to cavitand 1. Studies involved six Hofmeister salts covering the range of salting-in to strongly salting-out. The latter were found to reduce affinity. The cause of this was competitive binding of the weakly solvated anion to the hydrophobic pocket of the host. At the other extreme of the Hofmeister series, salts increased guest affinity. Two factors for this were evident. At low concentrations the data fitted a previously reported model that accounts for cation condensation to the outer carboxylates of the host (Carnagie, R.; Gibb, C. L. D.; Gibb, B. C., Angew. Chem., Int. Ed. 2014, 53 (43), 11498-11500). At higher concentrations, an as of yet unidentified contribution was observed that was noted to be guest dependent. Midcontinuum salts such as NaClO3 were found to enhance affinity at low concentrations, but weaken it at high concentrations; a nonmonotonic trend attributed to the aforementioned competing phenomena. In combination with previous work, the data presented here reveal that the Hofmeister effect evident in this system can be mostly attributed to solute-salt interactions.
Smoothelin is a cytoplasmic protein expressed in differentiated smooth muscle cells. Immunohistochemical evaluation of smoothelin has previously been reported in gastrointestinal (GI) smooth muscle tumors, but has yet to be studied in smooth muscle tumors of uterine and other soft tissue origin. DOG1 expression is reported to be specific for GI stromal tumors; however, variable expression has been reported in leiomyosarcomas (LMS) depending on site of origin. Overexpression of p16 is common in LMS of uterine and other sites of origin, but has not been correlated with tumor grade. This study explores the differential expression of these markers, as well as caldesmon, in LMS cases to assess diagnostic utility. Using tissue microarrays and cases from Tulane Medical Center and Medical College of Wisconsin, expression of smoothelin, DOG1, caldesmon, and p16 was evaluated by immunohistochemistry in 87 cases of LMS. The cases were subdivided by location of origin into uterine (N=31) and nonuterine (N=56) with 10 of the nonuterine of GI origin, as well as by grade into low grade (N=27) and intermediate and high grade (N=60). Differential expression among different grades and locations was evaluated. The same markers were evaluated in atypical leiomyoma cases (N=4) and 1 smooth muscle tumor of uncertain malignant potential case (N=1). Smoothelin expression was also assessed in 20 benign uterine leiomyomas. Weak DOG1 expression is rare but possible in extrauterine LMS. Expression of p16 is common in both uterine and extrauterine LMS, and more frequent in higher grades. Expression of smoothelin in this study differed depending on tumor type, grade, and site of origin. All leiomyomas and most atypical leiomyomas showed cytoplasmic positivity for smoothelin, whereas only 5% of LMS had cytoplasmic expression. The study suggests smoothelin may be downregulated in the cytoplasm of malignant smooth muscle tumor cells and may serve as a supportive aid in the distinction of LMS from benign smooth muscle tumors in cases where it is difficult by morphology alone.
Poorly differentiated thyroid carcinoma (PDTC) is an uncommon form of thyroid cancer, accounting for less than 5 % of all cases. It tends to be more clinically aggressive than differentiated thyroid cancers. While thyroidectomy is the mainstay of treatment, radioactive iodine plays an adjunctive role as well as TSH suppression with thyroid hormone. Some patients with advanced disease, may benefit from external beam radiation and/or systemic therapy. Case Description: A 94-year-old man presents with a left neck mass. His past medical history is significant for controlled hypertension. He notices a slowly growing mass while shaving over few months. He has no dysphagia, hoarseness, or shortness of breath. He has no history of radiation exposure and no family history of thyroid disease. A CT of the neck with contrast shows multiple pathologic appearing lymph nodes on the left side of the neck. The largest measures 5.4 x 4 x 3.9 cm, displacing the carotid space, and indenting the left internal jugular vein. The left lobe of the thyroid is heterogeneously enlarged compared to the right lobe with multiple irregular hypo-enhancing nodules. A fine-needle aspiration of the left cervical lymph node is positive for malignant large cells in sheets and clusters. Some clusters have a vague papillary/trabecular type arrangement. A total thyroidectomy and left level II-IV neck dissection is performed. Pathology shows multifocal poorly differentiated papillary thyroid carcinoma measuring 2.2 cm in greatest dimension with extensive necrosis. There is a background of lymphocytic thyroiditis. There is extensive vascular invasion (>4 foci) and extra-thyroidal extension invading only the strap muscles. There is metastasis to 7 of 12 examined lymph nodes. The largest metastatic deposit at level III measures 2.8 cm with extra-nodal extension. Tumor is negative for BRAF-V600, NRAS and TERT. His postoperative labs are as follows: TSH 346 (post-rhTSH) uiu/ml (0.5-5.0), free T4 0.87 ng/dl (0.6-1.15),Tg 1.0 ng/ml and anti-Tg <0.9 iu/ml. Adjuvant therapy with 125 mCi of I-131 is performed as well as thyroid replacement with levothyroxine 100 mcg daily. A whole-body scan shows residual uptake in the thyroid bed and increased uptake to the left of the thyroid bed. FDG PET scan shows 2 left parapharyngeal nodes with SUV of 6.94 (0.8 cm), SUV of 3.73 (1.8 cm). There is a focus of increased activity at lateral left thyroid bed SUV of 4.59. There is a right mediastinal paratracheal lymph node with SUV of 9.79 measures 1.5 x 1.2 cm. Considering patient age, external beam radiation is deferred with patient agreement as the risk outweighs the benefit. Patient will be followed by imaging closely. Conclusion: PDTC is an uncommon form of thyroid cancer. These tumors generally do not produce thyroglobulin and close monitoring with imaging is essential to detect early metastatic disease. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstra...
While infection should always lead the differential when a patient with AIDS presents with fever, inflammatory and malignant aetiologies should also be considered. With profound immunocompromise, malignancies can develop as sequelae of viral oncogene expression. Human herpesvirus 8 (HHV-8) infection drives several AIDS-related cancers including Kaposi sarcoma (KS), multicentric Castleman disease and primary effusion lymphoma (PEL), which can present simultaneously with variable clinical features. Herein, we describe a case of synchronous visceral KS and extracavitary PEL in a patient with AIDS. The patient was treated with systemic chemotherapy and remains in remission after four cycles. We review other cases of copresenting HHV-8-related malignancies, explore the salient pathomechanisms and clinical features of these cancers and discuss treatment strategies.
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