In ovarian neoplasms, BRAF, but not KRAS, mutations are restricted to low-grade serous tumours

Genes of the RAF family, which mediate cellular responses to growth signals, encode kinases that are regulated by RAS and participate in the RAS/RAF/MEK/ERK/MAP-kinase pathway. Activating mutations in BRAF have recently been identified in melanomas, colorectal cancers, and thyroid and ovarian tumours. In the present study, an extensive characterization of BRAF and KRAS mutations has been performed in 264 epithelial and non-epithelial ovarian neoplasms. The epithelial tumours ranged from adenomas and borderline neoplasms to invasive carcinomas including serous, mucinous, clear cell, and endometrioid lesions. It is shown that BRAF mutations in ovarian tumours occur exclusively in low-grade serous neoplasms (33 of 91, 36%); these included serous borderline tumours (typical and micropapillary variants), an invasive micropapillary carcinoma and a psammocarcinoma. KRAS mutations were identified in 26 of 91 (29.5%) low-grade serous tumours, 7 of 49 (12%) high-grade serous carcinomas, 2 of 6 mucinous adenomas, 22 of 28 mucinous borderline tumours, and 10 of 18 mucinous carcinomas. Of note, two serous borderline tumours were found to harbour both BRAF and KRAS mutations. The finding that at least 60% of serous borderline tumours harbour mutations in two members of the ERK-MAP-kinase pathway (BRAF 36%, KRAS 30%) compared with 12% of high-grade serous carcinomas (BRAF 0%, KRAS 12%) indicates that the majority of serous borderline tumours do not progress to serous carcinomas. Furthermore, no BRAF mutations were detected in the other 173 ovarian tumours in this study.     

Living unrelated donor kidney transplantation between spouses

From November 3, 1975 to November 3, 1990, 874 kidney transplants were performed at our centers. Of these, 675 (77.2%) were from living donors and 199 (22.8%) were from cadaver donors. Five hundred eighty (66.4%) of the living donors were first degree related while 99 (11.3%) were unrelated or second degree related donors, 29 of which were spouses. All donor recipient pairs were ABO-compatible, with the exception of one pair. Donor recipient relations were wife to husband in 25 cases and husband to wife in 4 cases. All were first grafts and started functioning during surgery. In this series, the follow-up for the recipients was 4 to 64 months (mean 33.5 ± 4.5 months). One-year patient survival and graft survival rates were 92.4% and 81.9%, respectively. Two-year patient survival and graft survival rates were 92.4% and 78.2%, respectively. The single ABO-incompatible case is also doing well, 21 months postoperatively. This study demonstrates that the interspouse kidney transplantation may be used when cadaver organ shortage is a problem. While providing the couple with a better quality of life, interspouse kidney transplantation also enables the couple to share the joy of giving and receiving the gift of life from one another.

---

Resumen En nuestro centro se efectuaron 874 trasplantes renales entre noviembre 3 de 1975 y noviembre 3 de 1990; 675 (77.2%) fueron de donantes vivos y 199 (22.8%) de donantes cadavéricos; 580 (66.4%) de los donantes vivos fueron familiares de primer grado y 99 (11.3%) fueron donantes no relacionados familiarmente o familiares de segundo grado, de los cuales 29 eran cónyuges. Todas las parejas donante-recipiente exhibieron compatibilidad ABO, con excepción de una. La relación donante-recipiente fue esposa a esposo en 25 casos y esposo a esposa en 4 casos. Todos los injertos eran de primera vez y todos comenzaron a funcionar en la mesa de cirugía. El seguimiento osciló entre 4 y 64 meses (33.5 ± 4.5). Las tasas de sobrevida a un año del paciente y del injerto fueron 92.4% y 81.9% respectivamente; las tasas a dos años fueron 92.4% y 78.2% respectivamente. El único caso ABO no compatible también se encuentra bien, a 21 meses en la actualidad. El presente estudio demuestra que el trasplante renal entre esposos puede ser utilizado cuando haya escases de órganos cadavéricos. Al tiempo que permite una mejor calidad de vida, el procedimiento da a la pareja la oportunidad de gozar el hecho de otorgar y de recibir el regalo de la vida entre uno y otro.

---

Résumé Nous avons effectué 874 transplantations rénales dans nos centres de transplantation entre le 3 Nov, 1975 et le 3 Nov, 1990. Parmi celles-ci, 675 (77.2%) provenaient de donneurs vivants et 199 (22.8%) des reins provenaient de cadavres. Cinq cent quatre vingt des donneurs vivants (66.4%) étaient parents au premier degré alors que 99 (11.3%) étaient parents au 2è degré ou n'étaient pas parents, parmi lesquels 29 étaient des époux. Tous les couples donneur/receveur, sauf un, étaient compatibles dans le système ABO. Le couple donneur/receveur était femme à mari dans 25 cas et mari à femme dans quatre. Il s'agissait dans tous les cas d'une première greffe et qui a commencé à bien fonctionner sur la table d'opération. Dans cette série, le suivi des receveurs allait de 4 à 64 (33.5 ± 4.5) mois. Les taux de survie des malades et des greffes à un an étaient respectivement de 92.4% et 81.9%. Les taux de survie des malades et des greffes à deux ans étaient respectivement de 92.4% et 78.2%. Le seul cas avec incompatabilité ABO va très bien avec un recul de 21 mois. Cette étude montre que la transplantation entre époux est une solution valable en cas de manque de reins. En plus d'améliorer la qualité de survie du receveur et par là même du couple, cette variété de transplantation donne également au couple la possibilité d'avoir la joie de donner et de recevoir un cadeau de vie de leur époux.

     

Quercetin sensitizes cells in a tumour-like low pH environment to hyperthermia.

Quercetin has been shown to act as a hyperthermia sensitizer by inhibiting the synthesis of heat shock protein 70 (HSP70) in a variety of tumour cell lines. It is most effective under conditions of low pH. This study was designed to test the hypothesis that quercetin suppresses thermotolerance development in cells adapted to growth at low pH and renders them as responsive as acutely acidified cells to hyperthermia-induced cytotoxicity. Chinese hamster ovarian carcinoma cells (OvCa) were exposed to 42 degrees C hyperthermia and/or quercetin (50-200 mm) at their growth pH of either 7.3 or 6.7 or after acute acidification from 7.3 to 6.7. Thermotolerance development was measured by colony survival. HSP70 synthesis and total protein synthesis were measured by radioactive precursor pulse labelling techniques. Quercetin, in a concentration-dependent manner, reduced the rate of total protein synthesis and increased cytotoxicity equally after acute acidification to pH 6.7 or growth at pH 6.7 at 37 degrees C, and to a greater extent than it did in cells at pH 7.3. At 42 degrees C, 100 mm quercetin inhibited total protein synthesis, HSP70 synthesis and thermotolerance development to a similar extent in cells grown at pH 6.7 or acutely acidified to pH 6.7. In contrast, quercetin reduced but did not completely inhibit HSP70 synthesis and thermotolerance development in cells grown and heated at pH 7.3. These results support the hypothesis that quercetin can specifically reduce thermotolerance development in tumour cells adapted to growth at pHe 6.7 so that they respond similarly to acutely acidified cells. Since many tumours are adapted to growth at low pH and may resist a wide variety of therapeutic modalities, inhibition of thermotolerance expression by quercetin may not only enhance the response to hyperthermia but the response to commonly used therapies such as chemotherapy and radiation.     

Targeted vessel reconstruction in non‐contrast‐enhanced steady‐state free precession angiography

Image quality in non‐contrast‐enhanced (NCE) angiograms is often limited by scan time constraints. An effective solution is to undersample angiographic acquisitions and to recover vessel images with penalized reconstructions. However, conventional methods leverage penalty terms with uniform spatial weighting, which typically yield insufficient suppression of aliasing interference and suboptimal blood/background contrast. Here we propose a two‐stage strategy where a tractographic segmentation is employed to auto‐extract vasculature maps from undersampled data. These maps are then used to incur spatially adaptive sparsity penalties on vascular and background regions. In vivo steady‐state free precession angiograms were acquired in the hand, lower leg and foot. Compared with regular non‐adaptive compressed sensing (CS) reconstructions (CS_low), the proposed strategy improves blood/background contrast by 71.3 ± 28.9% in the hand (mean ± s.d. across acceleration factors 1–8), 30.6 ± 11.3% in the lower leg and 28.1 ± 7.0% in the foot (signed‐rank test, P < 0.05 at each acceleration). The proposed targeted reconstruction can relax trade‐offs between image contrast, resolution and scan efficiency without compromising vessel depiction. Copyright © 2016 John Wiley & Sons, Ltd.     

Discrimination between non-functioning pituitary adenomas and hypophysitis using machine learning methods based on magnetic resonance imaging‑derived texture features

Purpose

Hypophysitis is a heterogeneous condition that includes inflammation of the pituitary gland and infundibulum, and it can cause symptoms related to mass effects and hormonal deficiencies. We aimed to evaluate the potential role of machine learning methods in differentiating hypophysitis from non-functioning pituitary adenomas.

Methods

The radiomic parameters obtained from T1A-C images were used. Among the radiomic parameters, parameters capable of distinguishing between hypophysitis and non-functioning pituitary adenomas were selected. In order to avoid the effects of confounding factors and to improve the performance of the classifiers, parameters with high correlation with each other were eliminated. Machine learning algorithms were performed with the combination of gray-level run-length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray-level co-occurrence entropy.

Results

A total of 34 patients were included, 17 of whom had hypophysitis and 17 had non-functioning pituitary adenomas. Among the 38 radiomics parameters obtained from post-contrast T1-weighted images, 10 tissue features that could differentiate the lesions were selected. Machine learning algorithms were performed using three selected parameters; gray level run length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray level co-occurrence entropy. Error matrices were calculated by using the machine learning algorithm and it was seen that support vector machines showed the best performance in distinguishing the two lesion types.

Conclusions

Our analysis reported that support vector machines showed the best performance in distinguishing hypophysitis from non-functioning pituitary adenomas, emphasizing the importance of machine learning in differentiating the two lesions.