Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis.

PURPOSE: Thymic epithelial tumors (TET) are rare epithelial neoplasms of the thymus with considerable histologic heterogeneity. This retrospective study focused on the correlation of WHO-defined TET histotypes with survival and tumor recurrence in a large cohort of patients receiving different modes of treatment. PATIENTS AND METHODS: Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients received adjuvant chemotherapy. RESULTS: Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P <.01). CONCLUSION: The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs.     

Overexpression of the cytochrome p450 activator hpr6 (heme-1 domain protein/human progesterone receptor) in tumors.

OBJECTIVE: Hpr6 (heme-1 domain protein/human progesterone receptor) is one of a family of proteins that are implicated in progesterone metabolism, resistance to genotoxic agents and steroid biosynthesis. Because these processes are frequently misregulated in tumors, we have examined the expression of Hpr6 in a group of clinical tumor samples and cancer cell lines. METHODS: Hpr6 expression was analyzed by Western blot in extracts from breast, cervix, colon and thyroid cell lines and in nonmalignant and adjacent tumor tissue from breast, colon and thyroid. Hpr6 localization was determined by immunofluorescence. RESULTS: Hpr6 expression is significantly elevated in breast tumors in comparison with matched nonmalignant tissue and demonstrated limited overexpression in colon and thyroid tumors. Hpr6 is strongly expressed in a panel of tumor cell lines originating from breast, thyroid and colon. Hpr6 localizes to the perinuclear region of the cell, consistent with a role in cell detoxification, signaling and/or sterol synthesis. CONCLUSIONS: Hpr6 homologues regulate cytochrome P450 proteins implicated in hormone, steroid and xenobiotic chemical metabolism. These are the first studies linking Hpr6 expression to cancer progression and cellular survival. Our results suggest that Hpr6 is an important marker for cancer progression and a potential anticancer therapeutic target.     

Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth,Tolerability, Safety,and Gut Microbiome in Infants with Cow’s Milk Protein Allergy

This open-label, non-randomized, multicenter trial (Registration: {"type":"clinical-trial","attrs":{"text":"NCT 03661736","term_id":"NCT03661736"}}NCT 03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow’s milk protein allergy (CMPA). Term infants aged 1–8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks; 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from –0.31 at the baseline to +0.28 at the 4-months’ follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.     

Material Extrusion of Structural Polymer–Aluminum Joints—Examining Shear Strength,Wetting, Polymer Melt Rheology and Aging

Generating polymer–metal structures by means of additive manufacturing offers huge potential for customized, sustainable and lightweight solutions. However, challenges exist, primarily with regard to reliability and reproducibility of the additively generated joints. In this study, the polymers ABS, PETG and PLA, which are common in material extrusion, were joined to grit-blasted aluminum substrates. Temperature dependence of polymer melt rheology, wetting and tensile single-lap-shear strength were examined in order to obtain appropriate thermal processing conditions. Joints with high adhesive strength in the fresh state were aged for up to 100 days in two different moderate environments. For the given conditions, PETG was most suitable for generating structural joints. Contrary to PETG, ABS–aluminum joints in the fresh state as well as PLA–aluminum joints in the aged state did not meet the demands of a structural joint. For the considered polymers and processing conditions, this study implies that the suitability of a polymer and a thermal processing condition to form a polymer–aluminum joint by material extrusion can be evaluated based on the polymer’s rheological properties. Moreover, wetting experiments improved estimation of the resulting tensile single-lap-shear strength.