Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatic mutations in the Tp53 tumor suppressor gene are the most commonly seen genetic alterations in cancer, and germline mutations in Tp53 predispose individuals to a variety of early-onset cancers. Development of appropriate translational animal models that carry mutations in Tp53 and recapitulate human disease are important for drug discovery, biomarker development and disease modeling. Current Tp53 mouse and rat models have significant phenotypic and genetic limitations, and often do not recapitulate certain aspects of human disease. We used a marker-assisted speed congenic approach to transfer a well-characterized Tp53-mutant allele from an outbred rat to the genetically inbred Fischer-344 (F344) rat to create the F344-Tp53tm1(EGFP-Pac)Qly/Rrrc (F344-Tp53) strain. On the F344 genetic background, the tumor spectrum shifted, with the primary tumor types being osteosarcomas and meningeal sarcomas, compared to the hepatic hemangiosarcoma and lymphoma identified in the original outbred stock model. The Fischer model is more consistent with the early onset of bone and central nervous system sarcomas found in humans with germline Tp53 mutations. The frequency of osteosarcomas in F344-Tp53 homozygous and heterozygous animals was 57% and 36%, respectively. Tumors were highly representative of human disease radiographically and histologically, with tumors found primarily on long bones with frequent pulmonary metastases. Importantly, the rapid onset of osteosarcomas in this promising new model fills a current void in animal models that recapitulate human pediatric osteosarcomas and could facilitate studies to identify therapeutic targets.
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PMID:Fischer-344 Tp53-knockout rats exhibit a high rate of bone and brain neoplasia with frequent metastasis. 2752

Background: Lymph node and distant metastases are known as the prognostic factor in renal
Asian Pac J Cancer Prev 2016 Jan 09
PMID:Clinical Factors Predictive of Metastases from Renal Cell Carcinomas 2788 Sep 93

Tumors of the lacrimal sac are rare but their recognition and early management are imperative, as they are locally invasive and potentially life-threatening. Because of their rarity, large clinical studies with statistically significant data on the natural course, management, and prognosis of these neoplasms are unavailable. Current practices are therefore based on a few case series and a small number of isolated case reports. Most tumors are primary and of epithelial origin (60-94%), of which 55% are malignant. Lacrimal sac tumors typically present with epiphora and a palpable mass over the medial canthus and are thus often erroneously diagnosed as chronic dacryocystitis. A full history with clinical and diagnostic workup is essential to plan treatment, which is often multi-disciplinary. Statistically significant associations have been shown with higher tumor staging and size with increased metastatic risk and lower survival rates. Management usually involves complete surgical resection with adjuvant radiotherapy and/or chemotherapy for malignant lesions. Long-term follow-up is required, as recurrences and metastases can occur many years after initial treatment.
Asia Pac J Ophthalmol (Phila)
PMID:Lacrimal Sac Tumors--A Review. 2839 37

Uveal melanoma is an intraocular malignancy that, depending on its size and genetic make-up, may lead to metastases in up to 50% of cases. Currently, no therapy has been proven to improve survival. However, new therapies exploiting immune responses against metastases are being developed. The primary tumor is well characterized: tumors at high risk of developing metastases often contain macrophages and lymphocytes. However, these lymphocytes are often regulatory T cells that may suppress immune response. Currently, immune checkpoint inhibitors have shown marked efficacy in multiple cancers (eg, cutaneous melanoma) but do not yet improve survival in uveal melanoma patients. More knowledge needs to be acquired regarding the function of T cells in uveal melanoma. Other therapeutic options are related to the biochemical pathways. Targeting the RAF-MEK-ERK pathway with small molecule MEK inhibitors abrogates the growth of UM cells harboring GNAQ/GNA11 Q209 mutations, suggesting that these aberrant G-protein oncogenes mediate, at least in part, their effect through this hallmark proliferation pathway. Other pathways are also implicated, such as those involving c-Jun and YAP. Further studies may show how interference in the different pathways may affect survival.
Asia Pac J Ophthalmol (Phila)
PMID:Uveal Melanoma: Identifying Immunological and Chemotherapeutic Targets to Treat Metastases. 2839 39

Approximately 90% of uveal melanoma develop in the choroid, with the remainder arising in the ciliary body or the iris. The treatment of uveal melanoma is aimed at conserving the eye and useful vision, and, if possible, preventing metastatic disease. Enucleation is now reserved for tumors that are large and/or involve the optic disc, having largely been replaced by various forms of radiotherapy (plaque brachy-therapy, proton beam or stereotactic radiotherapy) and laser therapy. Whereas iridectomy and iridocyclectomy are widely performed, transscleral exoresection of choroidal tumors is performed only in a few centers because it requires special skills and hypotensive anesthesia. Transretinal endoresection using vitrectomy equipment is easier but controversial because of concerns about tumor seeding. Long-term postoperative surveillance is necessary to identify and treat local tumor recurrence and any other complications, such as radiation-induced morbidity, and to provide counseling to the patient. Factors predicting metastasis include older age, large tumor size, ciliary body involvement, extraocular spread, epithelioid cytomorphology, chromosome 3 loss and chromosome 8q gain, class 2 gene expression profile, loss of BRCA1-associated protein-1 (BAP1), and the presence of inflammation. Prognostication is enhanced by multi-variable analysis combining clinical, histologic, and genetic factors, also taking the patient's age and sex into account. As there is a lack of options for treating metastases, much research is focused on identifying potential therapeutic targets.
Asia Pac J Ophthalmol (Phila)
PMID:Uveal Melanoma Treatment and Prognostication. 2856 48

Intraocular metastases almost invariably arise in the uveal tract, mostly in the posterior choroid. They are the most common type of intraocular malignancy and often the first sign of tumor dissemination. Choroidal metastases generally appear as a creamy white or pale yellow mass associated with subretinal fluid and may be multifocal and bilateral. The most common primary sites are breast and lung. Diagnosis is aided by a variety of tests, particularly ultrasonography and optical coherence tomography. Intraocular biopsy is useful in patients with clinical suspicion of uveal metastasis but no evidence of primary malignancy despite systemic evaluation. If systemic treatment fails to control the ocular tumor, a good response is usually achieved with local therapies such as external beam radiation therapy, photodynamic therapy, and transpupillary thermotherapy. The life expectancy of patients with choroidal metastases is generally poor but has been improving thanks to the therapeutic advances taking place.
Asia Pac J Ophthalmol (Phila)
PMID:Intraocular Metastases--A Review. 2839 45

Conjunctival tumors encompass a broad range of diagnoses. The 3 most important malignant tumors include ocular surface squamous neoplasia (OSSN) (14%), melanoma (12%), and lymphoma (7%). Conjunctival malignancies are rarely found in children. Regarding OSSN, pre-disposing conditions include chronic solar radiation, immune deficiency (HIV), organ transplant, autoimmune conditions, xeroderma pigmentosum, and chronic exposure to cigarette smoke. OSSN is managed surgically or with topical/injection immunotherapy or chemotherapy. Metastasis occurs in <1%. Regarding melanoma, predisposing conditions include primary acquired melanosis (PAM), chronic nevus, and chronic solar radiation. Treatment of PAM or nevus can prevent melanoma. Melanoma management involves surgical resection with clean margins and avoidance of direct tumor manipulation ("no touch" technique). The first surgery is most important, to minimize tumor seeding. Biomarkers including BRAF, TERT, and PTEN provide information regarding risk for metastasis and allow for targeted antibiomarker therapies. Ten-year risk for melanoma metastasis is 25%. Tumors >2 mm thickness or those located in fornix, caruncle, or orbit are at highest risk for metastasis. Regarding lymphoma, predisposing conditions include benign reactive lymphoid hyperplasia, immune deficiency (HIV), immune dysfunction, and chronic inflammation/infection (Helicobacter pylori, Chlamydia psittaci). The 4 most important subtypes include extranodal marginal zone lymphoma (ENMZL), follicular lymphoma, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma. Treatment includes surgical resection, cryotherapy, radiotherapy, systemic chemotherapy, or targeted anti-B-cell therapy (rituximab). Lymphoma-related survival (5-year) depends on subtype and ranges from 97% (ENMZL) to 9% (MCL). Recognizing conjunctival tumors and understanding predisposing factors, biomarkers, and treatment strategies are vital to patient outcomes.
Asia Pac J Ophthalmol (Phila)
PMID:Conjunctival Tumors: Review of Clinical Features, Risks, Biomarkers, and Outcomes--The 2017 J. Donald M. Gass Lecture. 2839 47

Solitary metastasis of a carcinoma to carpal bone is extremely rare. Metastases of renal cell carcinoma (RCC) usually occur in a multiple fashion and there has been no report to date of a solitary metastasis to trapezium from RCC. The tumor was excised and reconstructed with iliac bone transplantation. 2 years and 6 months after surgery, there is no local recurrence with minimal functional loss.
J Hand Surg Asian Pac Vol 2017 Jun
PMID:Metastasis of Renal Cell Carcinoma to the Trapezium. 2850 77

Retinoblastoma is a rare cancer in children, where in less than a century of dire mortality there has been a cure in industrialized countries. Unfortunately, mortality remains high in emerging countries. The evolution of treatment makes it possible to go further by preserving the eyeball but this must not be done at the cost of the reappearance of metastases. Herein we outline the evolution of treatment from the beginning of the 20th century until the last recent evolutions, trying to imagine what could be the future treatments. In this pathology, the ophthalmologist is a doctor who must cure his patient and enucleation is considered a failure. This situation should not lead to shizophrenic situations where to keep an eye one would take risks with the life of the child. New international classifications, international prospective multicentric studies, and the search for blood biomarkers that can predict the risk of micrometastases could allow for better stratification of patients.
Asia Pac J Ophthalmol (Phila)
PMID:Retinoblastoma: Update on Current Management. 2855 78

Background: Metastasis is important in survival and the quality of life of female breast cancer patie
Asian Pac J Cancer Prev 2017 06 25
PMID:Metastasis and its Related Factors in Female Breast Cancer Patients in Kerman, Iran 2866 69


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