Whole tumor RNA-sequencing and deconvolution reveal a clinically-prognostic PTEN/PI3K-regulated glioma transcriptional signature

The concept that solid tumors are maintained by a productive interplay between neoplastic and non-neoplastic elements has gained traction with the demonstration that stromal fibroblasts and immune system cells dictate cancer development and progression. While less studied, brain tumor (glioma) biology is likewise influenced by non-neoplastic immune system cells (macrophages and microglia) which interact with neoplastic glioma cells to create a unique physiological state (glioma ecosystem) distinct from that found in the normal tissue. To explore this neoplastic ground state, we leveraged several preclinical mouse models of neurofibromatosis type 1 (NF1) optic glioma, a low-grade astrocytoma whose formation and maintenance requires productive interactions between non-neoplastic and neoplastic cells, and employed whole tumor RNA-sequencing and mathematical deconvolution strategies to characterize this low-grade glioma ecosystem as an aggregate of cellular and acellular elements. Using this approach, we demonstrate that optic gliomas generated by altering the germlin

Detection of arenavirus in a peripheral odontogenic fibromyxoma in a red tail boa (Boa constrictor constrictor) with inclusion body disease

A captive bred red tail boa (Boa constrictor constrictor) was presented with a large intraoral mass originating from the buccal gingiva, attached to the right dentary teeth row. Based on the clinical features and histological examination, the diagnosis of a peripheral odontogenic fibromyxoma was made. Sections of liver biopsies and circulating lymphocytes contained relatively few eosinophilic intracytoplasmic inclusion bodies, indistinguishable from those observed in inclusion body disease-affected snakes. Inclusion bodies were not observed in cells comprising the neoplastic mass. Using reverse transcription polymerase chain reaction (RT-PCR), arenavirus was detected in the neoplastic tissue. Two years after surgical removal of the mass, recurrence of the neoplastic lesion was observed. Numerous large inclusion body disease inclusions were abundantly present in the neoplastic cells of the recurrent fibromyxoma. Sections of liver biopsies and circulating lymphocytes contained relatively few intracytoplasmic inclusions. The RT-PCR revealed the presence of arenavirus in blood, a liver biopsy, and neoplastic tissue. The present case describes the co-occurrence of an arenavirus infection and an odontogenic fibromyxoma in a red tail boa

Transurethral resection and surveillance of bladder cancer supported by 5-aminolevulinic acid-induced fluorescence endoscopy

Purpose: We determined whether neoplastic disease, which was missed under white light can be found during transurethral resection of bladder cancer by 5-aminolevulinic acid-induced porphyrin fluorescence. Materials and Methods: 5-Aminolevulinic acid-induced fluorescence endoscopy was carried out in 328 cases. A 3% 5-aminolevulinic acid solution was instilled intravesically in a mean time of 2.8 h before endoscopy, The fluorescence was excited by a special incoherent light source which provided blue light in addition to white light. Results: In 82 (25%) cases additional neoplastic lesions were found only because of their red porphyrin fluorescence which was induced by 5-aminolevulinic acid. 31% of these neoplastic foci which were found in normal and nonspecific inflamed mucosa had a poorly differentiated histology. Conclusions: 5-Aminolevulinjc acid facilitates detection of neoplastic disease during transurethral resection of bladder cancer and increases the accuracy of diagnosis

A systematic approach to cancer: evolution beyond selection.

Cancer is typically scrutinized as a pathological process characterized by chromosomal aberrations and clonal expansion subject to stochastic Darwinian selection within adaptive cellular ecosystems. Cognition based evolution is suggested as an alternative approach to cancer development and progression in which neoplastic cells of differing karyotypes and cellular lineages are assessed as self-referential agencies with purposive participation within tissue microenvironments. As distinct self-aware entities, neoplastic cells occupy unique participant/observer status within tissue ecologies. In consequence, neoplastic proliferation by clonal lineages is enhanced by the advantaged utilization of ecological resources through flexible re-connection with progenitor evolutionary stages

Subcellular Localization of Beta Catenin in Colorectal Non Neoplastic and Neoplastic Lesions

Loss of adenomatous polyposis coli (APC) function is typically an early event  in sporadic colorectal cancer (CRC) pathogenesis. The key tumor suppressor function of the APC  protein lies in its ability to destabilize free cytoplasmic beta catenin. This lead to the accumulation of nuclear beta catenin, and together with the DNA binding protein Tcf-4, function as a transcriptional activator. Accumulation of stabilized free  β-catenin is considered as an early event and perhaps initiating the process in intestinal tumorigenesis. Neoplastic transformation in the CRC associated chronic colitis is considered similar to the adenoma-carcinoma sequence in sporadic CRC. The distinguish feature from the CRC-related colitis is the difference in time and frequency changes. Loss of APC function, regarded as the beginning of a very common event in sporadic CRC, but the CRC associated chronic colitis generally occurs at the end of the dysplasia-carcinoma sequence. This research was conducted to determine the subcellular location of beta catenin expression in chronic colitis, colorectal adenomas and carcinomas that were evaluated by immunohistochemical staining. It can be concluded that beta-catenin is a component that plays a role in the development of the CRC and the subcellular location of beta-catenin can describe its oncogenic activity.&nbsp

Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non-palpable testicular lesions

The purpose of this study was to evaluate prospectively the accuracy of qualitative and strain ratio elastography (SE) in the differential diagnosis of non-palpable testicular lesions. The local review board approved the protocol and all patients gave their consent. One hundred and six patients with non-palpable testicular lesions were consecutively enrolled. Baseline ultrasonography (US) and SE were correlated with clinical and histological features and ROC curves developed for diagnostic accuracy. The non-palpable lesions were all ≤1.5 cm; 37/106 (34.9%) were malignant, 38 (35.9%) were benign, and 31 (29.2%) were non-neoplastic. Independent risk factors for malignancy were as follows: size (OR 17.788; p = 0.002), microlithiasis (OR 17.673, p < 0.001), intralesional vascularization (OR 9.207, p = 0.006), and hypoechogenicity (OR, 11.509, p = 0.036). Baseline US had 89.2% sensitivity (95% CI 74.6-97.0) and 85.5% specificity (95% CI 75.0-92.8) in identifying malignancies, and 94.6% sensitivity (95% CI 86.9-98.5) and 87.1% specificity (95% CI 70.2-96.4) in discriminating neoplasms from non-neoplastic lesions. An elasticity score (ES) of 3 out of 3 (ES3, maximum hardness) was recorded in 30/37 (81.1%) malignant lesions (p < 0.001). An intermediate score of 2 (ES2) was recorded in 19/38 (36.8%) benign neoplastic lesions and in 22/31 (71%) non-neoplastic lesions (p = 0.005 and p = 0.001 vs. malignancies). None of the non-neoplastic lesions scored ES3. Logistic regression analysis revealed a significant association between ES3 and malignancy (χ2 = 42.212, p < 0.001). ES1 and ES2 were predictors of benignity (p < 0.01). Overall, SE was 81.8% sensitive (95% CI 64.8-92.0) and 79.1% specific (95% CI 68.3-88.4) in identifying malignancies, and 58.6% sensitive (95% CI 46.7-69.9) and 100% specific (95% CI 88.8-100) in discriminating non-neoplastic lesions. Strain ratio measurement did not improve the accuracy of qualitative elastography. Strain ratio measurement offers no improvement over elastographic qualitative assessment of testicular lesions; testicular SE may support conventional US in identifying non-neoplastic lesions when findings are controversial, but its added value in clinical practice remains to be proven

Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index

Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs. The cfDNA fragments and integrity index significantly differentiated neoplastic versus non-neoplastic dogs (P<0.05), and allowed the distinction between benign and malignant lesions (P<0.05). Even if without statistical significance, the amount of cfDNA was also affected by tumor necrosis and correlated with tumor size and apoptotic markers expression. A significant (P<0.01) increase of Bcl-2 in malignant tumors was observed, and in metastatic CMTs the evasion of apoptosis was also suggested. This study, therefore, provides evidence that cfDNA could be a diagnostic marker in dogs carrying mammary nodules suggesting that its potential application in early diagnostic procedures should be further investigated

The chaperone TRAP1 as a modulator of the mitochondrial adaptations in cancer cells

Mitochondria can receive, integrate, and transmit a variety of signals to shape many biochemical activities of the cell. In the process of tumor onset and growth, mitochondria contribute to the capability of cells of escaping death insults, handling changes in ROS levels, rewiring metabolism, and reprograming gene expression. Therefore, mitochondria can tune the bioenergetic and anabolic needs of neoplastic cells in a rapid and flexible way, and these adaptations are required for cell survival and proliferation in the fluctuating environment of a rapidly growing tumor mass. The molecular bases of pro-neoplastic mitochondrial adaptations are complex and only partially understood. Recently, the mitochondrial molecular chaperone TRAP1 (tumor necrosis factor receptor associated protein 1) was identified as a key regulator of mitochondrial bioenergetics in tumor cells, with a profound impact on neoplastic growth. In this review, we analyze these findings and discuss the possibility that targeting TRAP1 constitutes a new antitumor approach

Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?

BACKGROUND: Our aim was to identify the pancreatic cancer diabetogenic peptide. METHODS: Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. RESULTS: A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. CONCLUSIONS: The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus