Anaplastic Thyroid Cancer and Follicular Thyroid Cancer-derived Exosomal Analysis Via Treatment of Lovastatin and Vildagliptin and Pilot Prognostic Study Via Urine Exosomal Biological Markers in Thyroid Cancer Patients
Anaplastic Thyroid Cancer and Follicular Thyroid Cancer-derived Exosomal Analysis Via Treatment of Lovastatin and Vildagliptin and Pilot Prognostic Study Via Urine Exosomal Biological Markers in Thyroid Cancer Patients
The investigators expected to enroll 30 patients with papillary, follicular or anaplastic
 thyroid cancer, and collect their urine samples before operation, immediately after
 operation, post-operative 3, 6 12 months. The investigators will analyze the urine exosomal
 proteins and probable biological markers. The investigators hope to find the prognostic
 biological markers via this prospective study. The investigators further hope to find newly
 therapeutic mechanism and medications for such patients with poorly-differentiated or
 anaplastic thyroid cancer.
Although papillary and follicular thyroid cancers are low-grade endocrine malignancy, they
 were fatal if the cancer cells were poorly-differentiated or anaplastic change. Prior
 researches indicated that one-third well-differentiated thyroid cancers could transform to
 poorly-differentiated patterns, even to be anaplastic thyroid cancer (ATC), a fatal
 malignancy, and no effective therapeutic strategies was noted, including surgical
 intervention, chemotherapy and radiotherapy. The poorly-differentiated or anaplastic change
 of thyroid cancer cells proliferates rapidly and always invades local tissues with distant
 metastasis. Cellular de-differentiation is the most pivotal cause for malignant
 transformation and invasion. De-differentiation usually in papillary thyroid cancer and
 follicular thyroid cancer, and definitely in ATC. The Poorly-differentiated thyroid cancer
 cell will rapidly proliferate and metastasize. The poorly-differentiated tumor cells lost
 apoptotic mechanism with de-differentiation, and such phenomenon is fatal for such patients.
 The investigators started research of thyroid cancer since 1999, and the investigators
 initially found TNF-α could induce cyto-morphological re-differentiation of thyroid cancer
 cells. Later, the investigators further found Lovastatin could induce re-differentiation of
 anaplastic thyroid cancer (ATC) cells in 25μM, but induce apoptosis in 50μM, in 2001. In
 2006, the investigators designed nude mice model, and found tumor will shrink via treatment
 of Lovastatin in 5 or 10 mg/kg/day, but tumor will proliferate significantly in 1 mg/kg/day.
 The investigators called this phenomenon as "Duality effects" of statins. In 2012, the
 investigators found FLOT1 and transketolase (TKT) as important regulatory factor of
 re-differentiation and proliferation in ATC cells, respectively. The investigators also found
 that inhibition of Dipeptidyl peptidase-4 (CD26) will influence proliferation of ATC cells.
 Exosomes are nanovesicels secreted into extracellular environments. A growing evidence
 suggests theat exosomes could be used as biomarkers to be the diagnosis and prognosis of
 malignant tumors. Exosomes are 50-100 nm diameters, and correspond to the intrluminal
 vesicles of endosomal multivesicular bodies. Because of their cellular orgins, exosomes have
 specific protein markers, like CD63, CD9, CD81 and heat shock protein (HSP). Urine was used
 to be the biosamples in the past five years in baldder cancer, prostate cancer, breast cancer
 and ovarian cancer. Urine sample is usually easy to obtain and non-invasive. Exosomes
 secreted by cells could micro-molecularly transfer messages between cells and to be
 biological markers of cancer. The investigators now found Vildagliptin and Lovastatin could
 influence tumor cells survival via exosomal proteins. For patients of thyroid cancer, the
 investigators could obtain the urine samples without invasive procedures. Furthermore, the
 investigators could find the biological markers and therapeutic targets via the exosomal
 expression in urine. On the continuing basis of ATC cells culture experiments, the
 investigators expected to enroll 30 patients with papillary, follicular or anaplastic thyroid
 cancer, and collect their urine samples before operation, immediately after operation,
 post-operative 3, 6 12 months. The investigators will analyze the urine exosomal proteins and
 probable biological markers. The investigators hope to find the prognostic biological markers
 via this prospective study. The investigators further hope to find newly therapeutic
 mechanism and medications for such patients with poorly-differentiated or anaplastic thyroid
 cancer.
Inclusion Criteria:

 -  Newly diagnosed patients with thyroid papillary, follicular and anaplastic thyroid
 cancer

 Exclusion Criteria:

 -  Thyroid papillary, follicular and anaplastic thyroid cancer with prior operation,
 chemotherapy, or isotope treatment, or target therapy.