Aged ; CD3 Complex ; metabolism ; Humans ; Immunohistochemistry ; Leukocyte Common Antigens ; metabolism ; Lymphoma, T-Cell, Peripheral ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Thyroid Neoplasms ; drug therapy ; metabolism ; pathology ; surgery

BRAF is one of the most important pro-oncogenes, which is mutated in approximately 8% of human tumors. The most common BRAF mutation is a valine-to-glutamate transition (V600E) that is expressed primarily in melanoma, colorectal cancer and thyroid carcinoma. MEK/ERK is constitutively activated in the cells expressing BRAFV600E, leading to tumor development, invasion, and metastasis. Therefore, BRAFV600E is a therapeutic target for melanoma and some other BRAFV600E tumors. Vemurafenib, a BRAFV600E inhibitor, which was approved by FDA for the treatment of late-stage melanoma in 2011, produces improved rates of overall and progression-free survival in patients with the BRAFV600E mutation, making a dramatic breakthrough in melanoma treatment. Vemurafenib is also an individual target drug based on genetic diagnosis. However, its therapeutic success is limited by the emergence of drug resistance. Therefore, it is important to explore the mechanisms underlying the resistance for developing new inhibitor drugs and for preventing or delaying the resistance evolution to BRAF inhibitor drugs. In this review, we described the role of BRAFV600E as an anti-tumor drug target and the development of BRAF inhibitors. We also discussed the mechanisms leading to resistance of BRAFV600E inhibitors. Furthermore, therapeutic strategies that might be employed to overcome acquired resistance were proposed.
Animals ; Antineoplastic Agents ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; genetics ; metabolism ; Drug Delivery Systems ; Drug Resistance, Neoplasm ; Humans ; Imidazoles ; therapeutic use ; Indoles ; therapeutic use ; Melanoma ; drug therapy ; genetics ; metabolism ; Mitogen-Activated Protein Kinase Kinases ; metabolism ; Mutation ; Oximes ; therapeutic use ; Proto-Oncogene Proteins B-raf ; antagonists & inhibitors ; genetics ; metabolism ; Sulfonamides ; therapeutic use ; Thyroid Neoplasms ; drug therapy ; genetics ; metabolism

Primary small cell carcinoma (SCC) of the breast, an exceedingly rare and aggressive tumor, is often characterized by rapid progression and poor prognosis. We report a case of primary SCC of the breast that was diagnosed through pathologic and immunohistochemical examinations. Computed tomography (CT) scans failed to reveal a non-mammary primary site. Due to the scant number of relevant case summaries, this type of tumor is proved to be a diagnostic and therapeutic challenge. Therefore, we also reviewed relevant literature to share expertise in diagnosis, clinicopathologic characteristics, treatment, and prognosis of this type of tumor. Future studies with more cases are required to define more appropriate treatment indications for this disease.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; diagnostic imaging ; drug therapy ; metabolism ; pathology ; CD56 Antigen ; metabolism ; Carboplatin ; administration & dosage ; Carcinoma, Intraductal, Noninfiltrating ; diagnostic imaging ; drug therapy ; metabolism ; pathology ; Carcinoma, Small Cell ; diagnostic imaging ; drug therapy ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Mammography ; Nuclear Proteins ; metabolism ; Phosphopyruvate Hydratase ; metabolism ; Synaptophysin ; metabolism ; Taxoids ; administration & dosage ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism ; Ultrasonography

We evaluated the efficacy of recombinant human thyroid-stimulating hormone (rhTSH) versus thyroid hormone withdrawal (THW) prior to radioiodine remnant ablation (RRA) in thyroid cancer. A systematic search of MEDLINE, EMBASE, the Cochrane Library, and SCOPUS was performed. Randomized controlled trials that compared ablation success between rhTSH and THW at 6 to 12 months following RRA were included in this study. Six trials with a total of 1,660 patients were included. When ablation success was defined as a thyroglobulin (Tg) cutoff of 1 ng/mL (risk ratio, 0.99; 95% confidence interval, 0.96-1.03) or a Tg cutoff of 1 ng/mL plus imaging modality (RR 0.97; 0.90-1.05), the results of rhTSH and THW were similar. There were no significant differences when ablation success was defined as a Tg cutoff of 2 ng/mL (RR 1.03; 0.95-1.11) or a Tg cutoff of 2 ng/mL plus imaging modality (RR 1.02; 0.95-1.09). When a negative 131I-whole body scan was used solely as the definition of ablation success, the effects of rhTSH and THW were not significantly different (RR 0.97; 0.93-1.02). Therefore, ablation success rates are comparable when RRA is prepared by either rhTSH or THW.
Catheter Ablation ; Clinical Trials as Topic ; Databases, Factual ; Humans ; Iodine Radioisotopes/*therapeutic use ; Radiopharmaceuticals/*therapeutic use ; Recombinant Proteins/biosynthesis/genetics/therapeutic use ; Risk ; Thyroglobulin/analysis/metabolism ; Thyroid Neoplasms/*drug therapy/ultrasonography ; Thyrotropin/genetics/metabolism/*therapeutic use ; Treatment Outcome ; Whole Body Imaging

No abstract available.
Fluorodeoxyglucose F18/diagnostic use ; Genetic Variation ; Humans ; Individualized Medicine/*methods ; Iodine Radioisotopes/*therapeutic use ; Molecular Imaging/methods ; Positron-Emission Tomography ; Symporters/biosynthesis/*metabolism ; Thyroid Neoplasms/*drug therapy/*genetics ; Tumor Microenvironment

Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.
Antigens, CD/metabolism ; Antineoplastic Agents/*pharmacology/therapeutic use ; Carcinoma, Embryonal/*drug therapy/metabolism ; Cell Differentiation/*drug effects ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Flavonoids/*pharmacology/therapeutic use ; Gene Expression Regulation, Neoplastic ; Genistein/pharmacology/therapeutic use ; Humans ; Kaempferols/pharmacology/therapeutic use ; Models, Biological ; Phenols/*pharmacology/therapeutic use ; Quercetin/pharmacology/therapeutic use ; Resorcinols/pharmacology/therapeutic use ; Stilbenes/pharmacology/therapeutic use ; Symporters/metabolism ; Thyroid Neoplasms/*drug therapy/metabolism