Targeted gene therapy has become a promising approach for lung cancer treatment. In our previous work, we reported that the targeted expression of microRNA-7 (miR-7) operated by thyroid transcription factor-1 (TTF-1) promoter inhibited the growth of human lung cancer cells in vitro and in vivo; however, the intervention efficiency needed to be further improved. In this study, we identified the core promoter of TTF-1 (from -1299 bp to -871 bp) by 5' deletion assay and screened out the putative transcription factors nuclear factor-1 (NF-1) and activator protein-1 (AP-1). Further analysis revealed that the expression level of NF-1, but not AP-1, was positively connected with the activation of TTF-1 core promoter in human non-small-cell lung cancer (NSCLC) cells. Moreover, the silencing of NF-1 could reduce the expression level of miR-7 operated by TTF-1 core promoter. Of note, we optimized four distinct sequences to form additional NF-1-binding sites (TGGCA) in the sequence of TTF-1 core promoter (termed as ^optTTF-1 promoter), and verified the binding efficiency of NF-1 on the ^optTTF-1 promoter by electrophoretic mobility shift assay (EMSA). As expected, the ^optTTF-1 promoter could more effectively drive miR-7 expression and inhibit the growth of human NSCLC cells in vitro, accompanied by a reduced transduction of NADH dehydrogenase (ubiquinone) 1α subcomplex 4 (NDUFA4)/protein kinase B (Akt) pathway. Consistently, ^optTTF-1 promoter-driven miR-7 expression could also effectively abrogate the growth and metastasis of tumor cells in a murine xenograft model of human NSCLC. Finally, no significant changes were detected in the biological indicators or the histology of some important tissues and organs, including heart, liver, and spleen. On the whole, our study revealed that the optimized TTF-1 promoter could more effectively operate miR-7 to influence the growth of human NSCLC cells, providing a new basis for the development of microRNA-based targeting gene therapy against clinical lung cancer.
Animals ; Humans ; Mice ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/metabolism* ; MicroRNAs/metabolism* ; Nuclear Proteins/metabolism* ; Thyroid Gland/pathology* ; Thyroid Nuclear Factor 1/genetics* ; Transcription Factors/metabolism*

Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some evidence that iodine-131 can induce liver injury . Here we report a rare case of drug-induced liver injury (DILI) caused by iodine-131 in a patient with regional lymph node metastasis after total thyroidectomy. A 47-year-old woman was admitted with elevated liver enzymes and symptoms of general weakness and nausea. Ten weeks earlier she had undergone a total thyroidectomy for papillary thyroid carcinoma and had subsequently been prescribed levothyroxine to reduce the level of thyroid-stimulating hormone. Eight weeks after surgery she underwent iodine-131 ablative therapy at a dose of 100 millicuries, and subsequently presented with acute hepatitis after 10 days. To rule out all possible causative factors, abdominal ultrasonography, endoscopic ultrasonography (on the biliary tree and gall bladder), and a liver biopsy were performed. DILI caused by iodine-131 was suspected. Oral prednisolone was started at 30 mg/day, to which the patient responded well.
Abdomen/diagnostic imaging ; Chemical and Drug Induced Liver Injury/*diagnosis/drug therapy ; Female ; Humans ; Iodine Radioisotopes/chemistry ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Middle Aged ; Prednisolone/therapeutic use ; Thyroid Neoplasms/drug therapy/surgery ; Thyroidectomy ; Thyroxine/therapeutic use ; Ultrasonography

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare type of thyroid malignancy and one of the most aggressive solid tumors, responsible for between 14% and 50% of the total annual mortality associated with thyroid cancer. METHODS: A retrospective study was made of all ATC cases diagnosed by biopsy in the Philippine General Hospital between 2008 and 2013. RESULTS: A total of 15 patients were identified, with a median age at diagnosis of 63 years. All tumors were at least 6 cm in size upon diagnosis. All patients had a previous history of thyroid pathology, presenting with an average duration of 11 years. Eleven patients presented with cervical lymphadenopathies, whereas seven exhibited signs of distant metastases, for which the lungs appeared to be the most common site. More than 70% of the patients presented with a rapidly growing neck mass, leading to airway obstruction. Only three patients were treated using curative surgery; the majority received palliative and supportive forms of treatment. In addition, only three patients were offered radiotherapy. Chemotherapy was not offered to any patient. Only two patients were confirmed to still be alive during the study period. The median survival time for the other patients was 3 months; in the majority of cases the patient died within the first year following diagnosis. CONCLUSION: Our experience with ATC demonstrated concordance with other institutions with respect to current clinical profile, presentation, and prognosis. An absence of distant metastases and lymph node involvement was associated with improved survival outcomes, whereas age at diagnosis and tumor size did not affect survival. Curative surgery offers the most effective means of prolonging survival. Radiotherapy and chemotherapy in combination with surgery represents a promising treatment strategy.
Airway Obstruction ; Biopsy ; Diagnosis ; Drug Therapy ; Hospitals, General* ; Humans ; Lung ; Lymph Nodes ; Mortality ; Neck ; Neoplasm Metastasis ; Pathology ; Philippines ; Prognosis ; Radiotherapy ; Retrospective Studies ; Thyroid Gland ; Thyroid Neoplasms*

Poorly differentiated thyroid carcinoma (PDTC) is a special type of thyroid carcinoma, the morphology and biological behavior of which are between well-differentiated and undifferentiated (anaplastic) carcinomas. Currently, the diagnosis of PDTC mainly relies on the pathological standards. Although "Turin standards" is commonly used, there is no generally accepted diagnostic criteria. Surgery is still the main treatment for PDTC, but the adjuvant therapies are in dispute. Age, tumor node metastasis (TNM) stage and integrity of surgical of PDTC are major factors that affect the prognosis. The identification of eosinophilic phenotype (hurthle cells) of PDTC is important. Some common immunohistochemical and molecular biomarkers, such as the insulin-like growth factor II mRNA-binding protein 3 (IMP3), E-cadherin and proliferating protein Ki67, may be helpful for distinguishing PDTC from other thyroid carcinoma. With the progress in studies regarding molecular markers for PDTC and the clinical characters of PDTC patients with large samples, the diagnosis for PDTC will greatly improved and the pathogenesis for PDTC will be elucidated.
Biomarkers, Tumor ; metabolism ; Cadherins ; metabolism ; Carcinoma ; pathology ; Combined Modality Therapy ; Humans ; Insulin-Like Growth Factor II ; metabolism ; Ki-67 Antigen ; metabolism ; Prognosis ; RNA-Binding Proteins ; metabolism ; Thyroid Neoplasms ; pathology

In the past century, there have been many attempts to treat cancer with low levels of electric and magnetic fields. We have developed noninvasive biofeedback examination devices and techniques and discovered that patients with the same tumor type exhibit biofeedback responses to the same, precise frequencies. Intrabuccal administration of 27.12 MHz radiofrequency (RF) electromagnetic fields (EMF), which are amplitude-modulated at tumor-specific frequencies, results in long-term objective responses in patients with cancer and is not associated with any significant adverse effects. Intrabuccal administration allows for therapeutic delivery of very low and safe levels of EMF throughout the body as exemplified by responses observed in the femur, liver, adrenal glands, and lungs. In vitro studies have demonstrated that tumor-specific frequencies identified in patients with various forms of cancer are capable of blocking the growth of tumor cells in a tissue- and tumor-specific fashion. Current experimental evidence suggests that tumor-specific modulation frequencies regulate the expression of genes involved in migration and invasion and disrupt the mitotic spindle. This novel targeted treatment approach is emerging as an appealing therapeutic option for patients with advanced cancer given its excellent tolerability. Dissection of the molecular mechanisms accounting for the anti-cancer effects of tumor-specific modulation frequencies is likely to lead to the discovery of novel pathways in cancer.
Carcinoma, Hepatocellular ; therapy ; Cell Proliferation ; radiation effects ; Electromagnetic Fields ; Humans ; Liver Neoplasms ; therapy ; Magnetic Field Therapy ; adverse effects ; Neoplasms ; diagnosis ; pathology ; therapy ; Radiation Dosage ; Radio Waves ; Thyroid Neoplasms ; therapy ; Treatment Outcome

Here, we present the case of a patient with bilateral choroidal metastases with extraocular extension in one eye. Metastasis of papillary thyroid carcinoma to the uvea is extremely rare, with only 6 patients reported in the literature. A 62-year-old man with a prior history of papillary thyroid carcinoma suffered the rapid loss of vision in his right eye. He had neovascular glaucoma, total retinal detachment, and a solitary choroidal mass. A month later, his left visual acuity also decreased because of a small macular choroidal mass. The right eye was enucleated and a nodular lesion over the sclera representing extraocular extension was observed. This tumor and the intraocular lesion were composed of papillary excrescences and cystic spaces and stained positively for thyroid transcription factor 1 and thyroglobulin, all confirming the diagnosis of metastatic papillary thyroid carcinoma. The tumor in the left eye was successfully treated with diode laser transpupillary thermotherapy. The patient expired within a month as a result of widespread pulmonary metastases. Papillary thyroid carcinoma may metastasize to the uvea bilaterally, cause rapid visual function loss, erode the sclera, and may extend outside the globe similar to choroidal melanoma. This aggressive ocular involvement was associated with a dismal prognosis in our patient.
Carcinoma/*pathology/therapy ; Choroid/*pathology ; Choroid Neoplasms/*secondary/therapy ; Humans ; Hyperthermia, Induced ; Lung Neoplasms/secondary ; Male ; Middle Aged ; Sclera/*pathology ; Thyroid Neoplasms/*pathology/therapy

The three-level recurrence stratification of differentiated thyroid carcinoma (DTC) has attracted wide attention since its introduction in 2009 American Thyroid Association guidelines. Among these three levels, the postoperative treatment of DTC with intermediate recurrence risk is highly controversial. This article summarizes the relevant advances and controversies in this field.
Humans ; Iodine Radioisotopes ; therapeutic use ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Period ; Risk Adjustment ; Thyroid Neoplasms ; pathology ; therapy

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

Oncologists and scientists in the field of head and neck cancer exchanged their research findings and clinical experiences in the Sino-USA Symposium on Head and Neck Cancer, which was held January 6-7, 2012 in Guangzhou, China. The symposium was jointly organized by Sun Yat-sen University Cancer Center (SYSUCC) and the University of Texas MD Anderson Cancer Center (MDACC). The Guangdong Provincial Anti-Cancer Association and the Chinese Journal of Cancer also helped in organizing the conference. Speakers were from China (SYSUCC, the Chinese University of Hong Kong, Tianjin Medical University Cancer Institute and Hospital, and Fudan University Shanghai Cancer Center) and the United States (MDACC). The presentations covered most kinds of head and neck cancers and included both basic and clinical research progress. In particular, NPC was discussed in depth. The symposium explored the reality that cancer is complex and numerous questions remain to be answered, even though there has already been an enormous effort into research. International exchanges of experience and in-depth cooperation are definitely needed to improve our capability of caring for cancer patients. In this article, we provide highlights of the presentations.
Carcinoma, Squamous Cell ; genetics ; Combined Modality Therapy ; Drug Delivery Systems ; Head and Neck Neoplasms ; drug therapy ; etiology ; genetics ; pathology ; surgery ; Humans ; Nasopharyngeal Neoplasms ; genetics ; pathology ; therapy ; Thyroid Neoplasms ; epidemiology

OBJECTIVE: To investigate the feasibility of salvage surgery of thyroid carcinoma in advanced stage with common carotid artery involvement. METHODS: Reviewed 4 cases of advanced-stage thyroid carcinoma treated in the Department of Otolaryngology, West China hospital from July 2006 to September 2009. CT revealed that the common carotid artery entrapped in the tumor without obvious anatomical space. 2 cases were proved to be low-differentiated squamous carcinoma pathologically and the rest 2 cases were papillary carcinoma. Total thyroidectomy, total laryngectomy and bilateral neck dissection were performed in 3 cases while in one case, total thyroidectomy, bilateral neck dissection and partial tracheal resection being performed. Adjacent prepared cervico-pectoral flap was used to reconstruct the defect of cervico-thoracic trachea. Rupture of common carotid artery in one case took place and was repaired by mere suture. One case of low differentiated squamous carcinoma was given postoperative chemotherapy and radiotherapy while the rest 3 cases given no adjuvant chemotherapy and radiotherapy. The follow-up time lasted from half a year to 2 years. RESULTS: Half a year postoperatively, the low-differentiated squamous carcinoma patient not receiving postoperative chemoradiotherapy suffered from lumber spinal metastasis, one year after operation he was still alive and half a year later lost follow-up, the other 3 patients were alive from half a year to 2 years postoperatively without any obvious clue of recurrence or remote metastasis. CONCLUSION Salvage surgery is still feasible in thyroid carcinoma in advanced stage with common carotid artery involvement. The larynx and trachea should be kept intact as possible but the reconstruction of the trachea defect is recommended to be less prior in the situation when carotid artery is involved in.
Adult ; Carcinoma, Papillary ; pathology ; surgery ; Carcinoma, Squamous Cell ; pathology ; surgery ; Carotid Artery, Common ; pathology ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Salvage Therapy ; Thyroid Neoplasms ; pathology ; surgery