Repolarization of tumor infiltrating macrophages and increased survival in mouse primary CNS lymphomas after XPO1 and BTK inhibition

Journal of Neuro-Oncology - Patients diagnosed with primary central nervous system lymphoma (PCNSL) often face dismal outcomes due to the limited availability of therapeutic options. PCNSL cells...     

PaO2 increases with coughing in patients with chronic lung disease

We considered if the cyanosis frequently observed during a cough attack in patients with chronic lung disease was due to worsening hypoxemia. To investigate the effects of cough on PaO2, we measured arterial blood gases before and after a voluntary coughing period of 45 sec, in 11 patients with Interstitial Lung Disease (ILD) and 14 patients with Chronic Obstructive Lung Disease (COPD). All patients significantly increased (p less than 0.05) their PaO2 (COPD: from 49 +/- 2 to 60 +/- 2 mmHg; ILD from 44 +/- 2 to 51 +/- 3 mmHg, mean +/- SD) and decreased their PaCO2. We conclude that stable patients with COPD and ILD increase their PaO2 with coughing most likely due to hyperventilation. The cyanosis observed could be due to peripheral circulatory effects of coughing.     

Allergy to eggs from duck and goose without sensitization to hen egg proteins

BACKGROUND: Eggs are among the foods most frequently causing allergy. Hen eggs are the most important. Those of other birds are of lesser significance. OBJECTIVE: We report an unusual case of food allergy after consumption of eggs from duck and goose in an adult patient without hen egg allergy. METHODS: Skin prick tests were performed with fresh white and yolk from eggs of duck and goose and egg white, egg yolk, ovalbumin, and ovomucoid from hen egg. Specific serum IgE was measured to hen egg proteins. SDS-PAGE and IgE immunoblotting were carried out with egg white extracts from hen, duck, and goose. RESULTS: Skin tests were positive to egg whites from duck and goose. The skin tests and specific serum IgE were negative to hen egg proteins. Immunoblotting demonstrated the presence of specific IgE to a proteic band of molecular weight around 45 kd. CONCLUSIONS: We report a patient with an IgE-mediated allergy to egg white from duck and goose without hen egg allergy. Ovalbumin seems to be the responsible protein. The antigenic determinant of this protein seems to be specific of order Anseriforme and it is not present in the ovalbumin of order Galliforme.     

Suprameatal extension of the retrosigmoid approach: microsurgical anatomy

OBJECTIVE: This study was conducted to determine whether removing the bony prominence located above the porus of the internal acoustic meatus, called the suprameatal tubercle, and surrounding bone using the retrosigmoid approach would aid in the exposure of tumors that are located predominantly in the cerebellopontine angle but that also extend into the middle cranial fossa in the region of Meckel's cave and thus avoid the need for a supratentorial craniotomy. METHODS: Thirty cerebellopontine angles from 15 cadaveric heads examined using 3 to 40x magnification provided the material for this study. A retrosigmoid craniotomy was completed and the exposure obtained before and after removing the suprameatal tubercle, and the surrounding bone was examined. In some cases, Meckel's cave and the tentorium lateral to the porus of Meckel's cave was opened to aid in the exposure. RESULTS: Removing the suprameatal tubercle and surrounding bone increased the exposure an average of 10.3 mm (range, 8.0-13.0 mm) forward of the exposure, which could be obtained without suprameatal drilling. The extent of bone removal was limited on the lateral side by the posterior and superior semicircular canals and their common crus. CONCLUSION: The suprameatal extension of the retrosigmoid approach will permit removal of some tumors that are located mainly in the posterior fossa but that extend into the middle fossa in the region of Meckel's cave. The exposure can be increased by opening the superior petrosal sinus as it crosses in the upper margin of the porus of Meckel's cave and by opening the tentorium lateral to Meckel's cave.     

Flow cytometric analysis of nuclear DNA content in oral leukoplakia

DNA ploidy has been studied in 31 paraffin-embedded specimens of oral leukoplakia and in 10 specimens of oral leukoplakia that have undergone malignant transformation after a 5-year observation period. Three out of 31 specimens (9.7%) showed an aneuploid DNA pattern, with DNA indices of 1.17, 1.28 and 1.32. It was not possible to establish a statistically significant difference of DNA ploidy related to the presence or absence of dysplasia. One out of the 10 oral leukoplakias that underwent malignant transformations had a multiploid pattern with DNA indices of 1.44 and 2.37. In this study the DNA index has not proved to be of value in the identification of dysplastic leukoplakia among the non-dysplastic ones.     

Plitidepsin has a cytostatic effect in human undifferentiated (anaplastic) thyroid carcinoma.

Undifferentiated (anaplastic) thyroid carcinoma is a highly aggressive human cancer with very poor prognosis. Although there have been a few studies of candidate treatments, the fact that it is an infrequent tumor makes it very difficult to design clinical trials. A strong association has been observed between undifferentiated thyroid carcinoma and TP53 mutations in numerous molecular genetic and expression studies. Plitidepsin (Aplidin, PharmaMar, Madrid, Spain) is a novel anticancer compound obtained from a sea tunicate. This compound has been reported to induce apoptosis independently of TP53 status. We investigated the actions of plitidepsin in human thyroid cancer cells. In initial experiments using primary cultured cells from a differentiated (papillary) carcinoma, we found that 100 nmol/L plitidepsin induced apoptosis, whereas lower doses were cytostatic. Because our aim was to study the effects of plitidepsin at clinically relevant concentrations, subsequent experiments were done with a dosage regimen reflecting plasma concentrations observed in previously reported clinical trials: 100 nmol/L for 4 hours, followed by 10 nmol/L for 20 hours (4(100)/20(10) plitidepsin). This plitidepsin dosage regimen blocked the proliferation of a primary undifferentiated/anaplastic thyroid carcinoma culture obtained in our laboratory and of a commercial cell line (8305C) obtained from an undifferentiated thyroid carcinoma; however, it did not induce apoptosis. The proportion of cells in the G(1) phase of the cell cycle was greatly increased and the proportion in the S/G(2)-M phases greatly reduced, suggesting that plitidepsin blocks G(1)-to-S transition. Levels of the cyclin D1/cyclin-dependent kinase 4/p21 complex proteins were decreased and, in line with this, the levels of unphosphorylated Rb1 increased. The decrease in cell cycle proteins correlated with hypoacetylation of histone H3. Finally, we did experiments to assess how rapidly tumor cells return to their initial pretreatment proliferative behavior after 4(100)/20(10) plitidepsin treatment. Cells from undifferentiated tumors needed more than 3 days to recover logarithmic growth, and after 7 days, cell number was still significantly lower than in control cultures. 4(100)/20(10) plitidepsin inhibited the growth in soft agar. Together, our data show that plitidepsin is able to block in vitro cell cycle progression at concentrations similar to serum concentrations observed in vivo, and that this effect is persistent for several days after plitidepsin removal. Whether plitidepsin will prove to be clinically useful in the treatment of undifferentiated thyroid cancers remains to be established. However, our results raise the possibility that plitidepsin might be effective alone or in combination with radiotherapy and/or other drug treatments.