- 18F-Fluoride PET/CT and 99mTc-MDP SPECT/CT can detect bone cancer at early stage in rodents. [Journal Article]
- LSLife Sci 2018 May 17
- Noninvasive imaging using positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT) are considered revolutionized approac...
Noninvasive imaging using positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/computed tomography (SPECT/CT) are considered revolutionized approaches to detect bone cancer. Both PET/CT and SPECT/CT technologies have advanced to permit miniaturization, which has provided the advantage of including animals as their own controls in longitudinal studies. The present study was designed to evaluate the potential of PET/CT and SPECT/CT as research tools to detect bone cancer in rats. We used a rat model of bone cancer induced by injecting Walker 256 tumor cells into the femoral cavity. Computed tomography demonstrated that rats presented a solid tumor at 15 days post injection (dpi). However, CT was not an effective method for identifying tumors at an earlier time point (8 dpi), when mechanical hyperalgesia (the most common symptom during bone cancer progression) had already initiated. At this early stage, PET/CT and SPECT/CT analysis detected higher uptake in the injected femur of the tracers 18F-Fluoride and 99mTc-Methyl diphosphonate (99mTc-MDP), respectively. These findings demonstrated for the first time that both 18F-Fluoride PET/CT and 99mTc-MDP SPECT/CT can detect cancer at early stages in rats and advocates for the PET/SPECT/CT as research tools to evaluate bone cancer in further longitudinal studies involving small animals.
- Ancient cancers and infection-induced oncogenesis. [Journal Article]
- IJInt J Paleopathol 2017 Aug 23
- Cancers have been reported in bone and soft tissue of ancient agricultural populations. Fossilized bones from prehistoric periods provide evidence of tumors but only one example of cancer. Difficulti...
Cancers have been reported in bone and soft tissue of ancient agricultural populations. Fossilized bones from prehistoric periods provide evidence of tumors but only one example of cancer. Difficulties in diagnosing the causes of lesions in mummified tissue and fossilized bone, and in interpreting the prevalence of cancers from remains, draw attention to the need for complementary approaches to assess the occurrence of cancer in ancient populations. This paper integrates current knowledge about pathogen induction of cancer with phylogenetic analyses of oncogenic pathogens, and concludes that pathogen-induced cancers were probably generally present in ancient historic and prehistoric human populations. Consideration of cancers in extant human populations and wildlife lends credence to this conclusion, with the caveat that the presence of cancers may depend on population-specific exposures to oncogenic parasites and carcinogens.
- Possible prostate cancer in northern Peru: Differential diagnosis, vascular anatomy, and molecular signaling in the paleopathology of metastatic bone disease. [Journal Article]
- IJInt J Paleopathol 2017 Feb 06
- This paper describes four possible cases of metastasized prostate cancer in archaeological human skeletons from the north coast of Peru spanning the Middle Sicán to Colonial eras (roughly A.D. 900-16...
This paper describes four possible cases of metastasized prostate cancer in archaeological human skeletons from the north coast of Peru spanning the Middle Sicán to Colonial eras (roughly A.D. 900-1600). Varying combinations of exuberant abnormal new bone formation and some abnormal bone loss affecting lumbar vertebrae and the bony sacrum were observed in these individuals. Detailed lesion descriptions are followed by a differential diagnosis that systematically eliminates pseudopathology, infectious diseases, sclerosing bone disorders, and most metastatic processes. However, metastasized prostate cancer cannot be rejected and is highly consistent with the observed lesions. Metastasized pancreatic, bladder, or carcinoid tumors represent additional, though far less likely, diagnostic options. Anatomical and molecular signaling factors further validate this differential diagnosis. The paravertebral venous plexus of Baston plays an anatomical role in the metastatic seeding of lumbar vertebra from prostate cancer. Further, abundant molecular signaling mechanisms upregulate multiple bone-forming mechanisms in prostate metastases, though initially such lesions may originate as lytic phenomena. These multiple lines of evidence help demonstrate a multi-level framework for explanation in paleopathology and especially to help better elucidate the complexities of ancient neoplastic diseases.
- Differential diagnosis of a neoplastic condition in a prehistoric juvenile individual from La Falda site, Northwest Argentina. [Journal Article]
- IJInt J Paleopathol 2016 Nov 22
- Bone neoplasms or tumors are of great interest for paleopathological studies due to their close relationship with health and survivorship as well as for their epidemiologic and demographic relevance....
Bone neoplasms or tumors are of great interest for paleopathological studies due to their close relationship with health and survivorship as well as for their epidemiologic and demographic relevance. However, the identification of these lesions in archaeological specimens is very uncommon. The aim of this paper is to report the case of skeleton R5 E#1 from the prehistoric cemetery La Falda, in the Northwest region of Argentina. During the osteopathological analysis of the skeletal series, proliferative lesions in several bones of the skeleton of a 7-10-year-old juvenile were observed (i.e., both scapulae; left clavicle, humerus, and ulna, both os coxae, femora, and fibulae, and right foot bones). Age-at-death estimation, location and distribution pattern, and morphological appearances of the lesions indicated that this juvenile suffered from a neoplastic condition. A comprehensive differential diagnosis was carried out, suggesting that these lesions were compatible with hereditary multiple osteochondromas. However, Ewing's sarcoma was not definitively ruled out as a probable diagnosis. Thus, this work adds new evidence to the existence of neoplastic conditions in the prehistoric populations of the Americas, and it contributes original data to perform a differential diagnosis for multiple proliferative lesions.
- A National Study of the Use of Asymptomatic Systemic Imaging for Surveillance Following Breast Cancer Treatment (AFT-01). [Journal Article]
- ASAnn Surg Oncol 2018 May 17
- CONCLUSIONS: Locoregional breast cancer patients undergo asymptomatic systemic imaging during follow-up despite guidelines recommending against it, but at lower rates than previously reported. Providers appear to use factors that confer increased recurrence risk to tailor decisions about systemic surveillance imaging, perhaps reflecting limitations of data on which current guidelines are based. ClinicalTrials.gov Identifier: NCT02171078.
- Site-specific expression of amine oxidases in breast cancer metastases. [Journal Article]
- TBTumour Biol 2018; 40(5):1010428318776822
- We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 12...
We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase ( p = 0.001), tumoral diamine oxidase ( p = 0.003), stromal diamine oxidase ( p = 0.047), and stromal monoamine oxidase B ( p = 0.002) were differentially expressed in different metastatic sites. Bone metastases showed low expression of lysyl oxidase, tumoral diamine oxidase, and stromal diamine oxidase. We observed high expression of lysyl oxidase in brain metastases, tumoral diamine oxidase in liver metastases, stromal diamine oxidase in lung metastases, and stromal monoamine oxidase B in bone metastases. Lysyl oxidase positivity was associated with progesterone receptor negativity ( p = 0.001), and monoamine oxidase A positivity was associated with human epidermal growth factor receptor-2 negativity ( p = 0.003) and the luminal A subtype ( p = 0.003). On univariate analysis shorter overall survival was associated with stromal diamine oxidase negativity ( p = 0.008), especially in lung metastases ( p = 0.025), and stromal monoamine oxidase B positivity ( p < 0.001). Stromal monoamine oxidase B positivity was an independent prognostic factor for shorter overall survival in multivariate Cox analysis (hazard ratio, 4.069; 95% confidence interval, 1.649-10.04; p = 0.002). Finally, in metastatic breast cancer, amine oxidase-related proteins were differentially expressed in a manner specific to metastatic site, and stromal monoamine oxidase B expression was correlated with prognosis.
- Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer. [Journal Article]
- EREndocr Relat Cancer 2018 May 17
- Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tande...
Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral DHT concentrations were significantly higher in the cancerous tissues compared to benign prostate (p<0.001). The tissue/serum ratios of androgens were highly variable between the patients, indicating individual patterns of androgen metabolism and/or uptake of androgens within the prostate tissue. An unsupervised hierarchical clustering analysis of intratissue androgen concentrations indicated that TMPRSS2-ERG positive patients have different androgen profiles compared to TMPRSS2-ERG negative patients. TMPRSS2-ERG gene fusion status was also associated with an enhanced androgen-regulated gene expression, along with altered intratumoral androgen metabolism, demonstrated by reduced testosterone concentrations and increased DHT/testosterone ratios in TMPRSS2-ERG positive tumors. TMPRSS2-ERG positive and negative prostate cancer specimens have distinct intratumoral androgen profiles, possibly due to activation of testosterone-independent DHT biosynthesis via the alternative pathway in TMPRSS2-ERG positive tumors. Thus, patients with TMPRSS2-ERG positive prostate cancer may benefit from novel inhibitors targeting the alternative DHT biosynthesis.
- Primary bone tumors and tumor like lesions of the ulna. [Journal Article]
- AOActa Orthop Traumatol Turc 2018 May 14
- CONCLUSIONS: Benign bone lesions tend to involve distal and proximal ends, malign bone lesions involve diaphysis mostly. Both benign and malignant diaphyseal lesions of the ulna have better postoperative results regarding the lesions at both ends of ulna. One should also take care of recurrences even after a decade from the primary surgery.
- Adolescent and young adult oncology patients in France: Heterogeneity in pathways of care. [Journal Article]
- PBPediatr Blood Cancer 2018 May 17; :e27235
- CONCLUSIONS: In France, pathways of care for AYAs are heterogeneous. It is necessary to organize a national network of expert centers with adequate medical skills and specific psychosocial support and facilities to provide the best possible care for these patients.
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- RhoA G17V is sufficient to induce autoimmunity and promotes T cell lymphomagenesis in mice. [Journal Article]
- BloodBlood 2018 May 16
- Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphoma...
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice). These mice had markedly reduced naïve T cells but relatively increased TFH cell populations. Surprisingly, naïve CD4 T-cells expressing RhoA G17V were hyperreactive to T-cell receptor stimulation. All tgRhoA mice developed autoimmunity that included a cellular infiltrate within ears and tails that was recapitulated in wild-type (WT) recipients after bone marrow transplantation. Older tgRhoA mice developed elevated serum titers of anti-double stranded DNA antibodies and renal immune complex deposition. RhoA G17V mice crossed with Tet2fl/fl; Vav-Cre+ mice, which delete Tet2 throughout the hematopoietic compartment, developed T-cell lymphomas that retained histologic and immunophenotypic features of AITL and had transcriptional signatures enriched for mTOR-associated genes. Transplanted tumors were responsive to the mTOR inhibitor everolimus, providing a possible strategy for targeting RhoA G17V. Taken together, these data indicate that RhoA G17V contributes to both neoplastic and paraneoplastic phenotypes like those observed in patients with TFH lymphomas.