[Progressive massive fibrosis in pneumoconiosis is mimicking lung malignancy on (18)F-FDGPET-CT: two cases report].

Occupational pneumoconiosis is one of the main occupational diseases in China. Progressive massive fibrosis in pneumoconiosis should be distinguished from lung cancer for their similar imaging features which is often identified by (18)F-FDG PET-CT in clinic. Here we reported two cases of pneumoconiosis. Both of them were suspected of carrying malignant tumors by preoperative PET-CT exam, however, nodules in these two patients were all proved to be benign by intraoperative pathology which suggested that there is false-positive possibility in the distinguishment of pneumoconiosis nodules by (18)F-FDG PET-CT.

Genomic and transcriptional heterogeneity of multifocal hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND METHODS: Whole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes. RESULTS: We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster. CONCLUSIONS: Our study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.

Synergism between arsenic trioxide and cyclopamine in the inhibition of PC3 cell survival via the Hedgehog signaling pathway.

Previous studies have shown that Hh signaling is overexpressed in the development and progression of prostate cancer (PCa), suggesting that Hh pathway inhibitors might be an effective strategy in the treatment of PCa. The combination of chemotherapeutic agents is one of the main approaches in cancer treatment, with the objective of improving efficacy. In the present study, we examined the effect of combing arsenic trioxide (ATO), a useful agent for Hedgehog-driven cancers, and cyclopamine (CYA), a classic Hh pathway inhibitor, on the suppression of PC3 cells (i.e., an androgen-independent PCa cell line). The combination of ATO and CYA more effectively inhibited the proliferation of PC3 cells than either single agent alone. In a xenograft mouse model, the combination of ATO and CYA significantly reduced tumor weight and volume in nude mice that were implanted with PC3 cells. The combination of ATO and CYA in PC3 cells resulted in a more distinct mode of Hh pathway inhibition and strengthened the S phase arrest. The present results indicate that a combination of ATO and CYA may be a rational strategy for treating PCa.

[Olivopontocerebellar atrophy: clinical analysis of 100 cases].

The clinical features in 100 patients suffered from olivopontocerebellar atrophy (OPCA) and their genetic trait were studied. The diagnosis was verified in all cases with computed tomography, demonstrating the atrophy of cerebellum and brainstem, vascular, neoplastic, infectious and any other organic disorder suspected were excluded. 53 out of 100 cases were sporadic (SOPCA) and the remainder (47 cases) was familial (FOPCA). The age of onset in SOPCA group was 36.1 +/- 14.95 (M +/- SD) in average, while in FOPCA group was 28.9 +/- 11.8. It seems that the symptoms in FOPCA group develop earlier than that in SOPCA group (P less than 0.05). All 47 cases of FOPCA group belong to 36 families in which altogether 166 persons were involved. According to pedigree patterns, there were 26 families inherited as autosomal dominant trait and probably so in another 5 families. Autosomal recessive trait could be confirmed in 2 families, in which the parents of proband were consanguineous, and in 3 other families autosomal recessive trait of inheritance was highly suspected. Anticipation was demonstrated in 26 families with dominant inheritance. Generally, ataxia and weakness of legs develop as initial symptoms in 88% of cases, then followed by dysarthria, and ataxia of upper extremities. The rapid alternating test of hand was impaired in 95% of patients, however, tension tremor was revealed only in 53% of patients. A method for assessing the ataxia quantitatively was proposed, our data suggest that the quantitative alternating test in the upper extremity and the measurement of base-width in lower extremity seem to be valuable in identifying the intensity of ataxia.