Selective anti-tumor activity of glutathione-responsive abasic site trapping agent in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive thyroid cancer with poor prognosis. Killing cancer cells by inducing DNA damage or blockage of DNA repair is a promising strategy for chemotherapy. It is reported that aldehyde-reactive alkoxyamines can capture the AP sites, one of the most common DNA lesions, and inhibit apurinic/apyrimidinic endonuclease 1(APE1)-mediated base excision repair (BER), leading to cell death. Whether this strategy can be employed for ATC treatment is rarely investigated. The aim of this study is to exploit GSH-responsive AP site capture reagent (AP probe-net), which responses to the elevated glutathione (GSH) levels in the tumor micro-environment (TME), releasing reactive alkoxyamine to trap AP sites and block the APE1-mediated BER for targeted anti-tumor activity against ATC. In vitro experiments, including MTT andγ-H2AX assays, demonstrate their selective cytotoxicity towards ATC cells over normal thyroid cells. Flow cytometry analysis suggests that AP probe-net arrests the cell cycle in the G2/M phase and induces apoptosis. Western blotting (WB) results show that the expression of apoptotic protein increased with the increased concentration of AP probe-net. Further in vivo experiments reveal that the AP probe-net has a good therapeutic effect on subcutaneous tumors of the ATC cells. In conclusion, taking advantage of the elevated GSH in TME, our study affords a new strategy for targeted chemotherapy of ATC with high selectivity and reduced adverse effects.

Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial.

BACKGROUND: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. METHODS: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. RESULTS: At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). CONCLUSIONS: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (NCT03451734).

Unexpected Phosphaturic Mesenchymal Tumor of the Femoral Head.

Osteonecrosis of femoral head (ONFH) is clinically common and easily diagnosed via imaging examination, especially when there is a definite cause, such as a fracture, long-term hormonotherapy, etc. However, some rare neoplastic lesions of the femoral head can mimic its image performance in some situations, leading to misdiagnosis. We present the case of a 57-year-old male with bone pain in the left hip joint that persisted for 2 years. CT and MRI images were performed and both were suggestive of ONFH. Unexpectedly, the histopathologic results of left proximal femur resection revealed the diagnosis of phosphaturic mesenchymal tumor (PMT), a rare mesenchymal tumor. His hip pain was obviously relieved after surgery, and the course of 1-year follow-up was uneventful.

Effect of Lugol's solution on 131I therapy efficacy in Graves' disease.

PURPOSE: Lugol's solution could control thyroid function and suppress 131I uptake in hyperthyroidism. This study aimed to investigate the appropriate time to withdraw Lugol's solution before 131I therapy (RIT) in Graves' disease (GD) patients, and how this should influence 131I uptake and RIT outcome. METHODS: Two groups (125 cases and 1805 cases) of GD patients received RIT, who were pre-treated with and without Lugol's solution (RI-CI group and RI group). The RI-CI group was further divided into the following sub-groups depending on the duration span between Lugol's solution withdrawal and RIT: sub-group A, 4-7 d (n = 49); sub-group B, 8-14 d (n = 41); and sub-group C, 15-30 d (n = 35). The highest radioactive iodine uptake rate (RAIUmax), effective half-life (Teff), TRAb, and free triiodothyronine (FT3) and free thyroxine (FT4) levels were compared, and therapeutic outcome was evaluated. RESULTS: There were no significant differences in RAIUmax, TRAb, and Teff among the four sub-groups (P > 0.05). Both FT3 and FT4 levels in sub-groups A and B were lower than those in group RI and sub-group C (P < 0.05). The outcome of non-hyperthyroidism (euthyroidism + hypothyroidism) in groups RI-CI and RI was significantly different at post-RIT month 1 and 3 (P < 0.05). However, intergroup differences at 6 and 12 months were not significant (P > 0.05). CONCLUSIONS: Withdrawal of Lugol's solution 4-7 or 8-14 d before RIT does not influence 131I uptake and RIT efficacy in GD. Moreover, in order to avoid a rapid increase in thyroid hormone levels at the same time, Lugol's solution should be withdrawn 4-7 d before RIT.

Bone metastases in newly diagnosed patients with thyroid cancer: A large population-based cohort study.

Background: Population-based estimates of the incidence and prognosis of bone metastases (BM) stratified by histologic subtype at diagnosis of thyroid cancer are limited. Methods: Using multivariable logistic and Cox regression analyses, we identified risk factors for BM and investigated the prognostic survival of BM patients between 2010 and 2015 via the Surveillance, Epidemiology, and End Results (SEER) database. Results: Among 64,083 eligible patients, a total of 347 patients with BM at the time of diagnosis were identified, representing 0.5% of the entire cohort but 32.4% of the subset with metastases. BM incidence was highest (11.6%) in anaplastic thyroid cancer (ATC), which, nevertheless, was highest (61.5%) in follicular thyroid cancer (FTC) among the subset with metastases. The median overall survival among BM patients was 40.0 months, and 1-, 3-, and 5-year survival rates were 65.2%, 51.3%, and 38.7%, respectively. Compared with papillary thyroid cancer (PTC), FTC (aOR, 6.33; 95% CI, 4.72-8.48), medullary thyroid cancer (MTC) (aOR, 6.04, 95% CI, 4.09-8.92), and ATC (aOR, 6.21; 95% CI, 4.20-9.18) significantly increased the risk of developing BM. However, only ATC (aHR, 6.07; 95% CI, 3.83-9.60) was independently associated with worse survival in multivariable analysis. Additionally, patients with BM alone (56.5%) displayed the longest median survival (66.0 months), compared with those complicated with one extraskeletal metastatic site (lung, brain, or liver) (35.2%; 14.0 months) and two or three sites (8.3%; 6.0 months). The former 5-year overall survival rate was 52.6%, which, however, drastically declined to 23.0% in patients with one extraskeletal metastatic site and 9.1% with two or three sites. Conclusion: Closer bone surveillance should be required for patients with FTC, MTC, and ATC, and extraskeletal metastases at initial diagnosis frequently predict a poorer prognosis.

Predictive Value of Clinical and Pathological Characteristics for Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma: A 16-year Retrospective Study.

Purpose: To assess predictive value of clinical and pathological characteristics for metastatic radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC) in early stage retrospectively. Methods: We studied 199 metastatic DTC patients who were divided into two groups (TgAb negative and TgAb positive). The stimulated Tg (Sti-Tg) at the first and second radioiodine therapy (RIT) were defined as Sti-Tg1 and Sti-Tg2, the suppressed Tg (Sup-Tg) were designated as Sup-Tg1 and Sup-Tg2, while the TgAb were defined as TgAb1 and TgAb2, respectively. Univariate analysis and Logistic regression were used to investigate the effects of 13 observed factors to predict RAIR-DTC. Results: In TgAb negative group, ROC curve analysis showed that cut-off values of age, Sti-Tg2/Sti-Tg1 and Sup-Tg2/Sup-Tg1 to predict RAIR-DTC were 40 years old, 57.0% and 81.0%, respectively. Age, extrathyroid invasion, Sti-Tg2/Sti-Tg1, Sup-Tg2/Sup-Tg1 and BRAF gene mutation were proved to be independent factors predicting RAIR-DTC. In TgAb-positive group, ROC curve analysis showed that cut-off values of age, TgAb1 and TgAb2/TgAb1 to predict RAIR-DTC were 55 years old, 297 IU/ml (14.8 times higher than the upper limit) and 53.6%, respectively. Conclusions: For TgAb-negative DTC, age over 40, extraglandular invasion, mutated BRAF gene, Sti-Tg decreased less than 43%, and Sup-Tg decreased less than 19% after the first two courses of RIT were independent predictors for RAIR-DTC. For TgAb-positive DTC, age over 55, extraglandular invasion, mutated BRAF gene, distant metastasis before RIT, TgAb level 14.8 times higher than the upper limit, TgAb dropped less than 46.4% after two courses of RIT were influencing factors.

Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy.

Exosomes are nanoscale monolayer membrane vesicles that are actively endogenously secreted by mammalian cells. Currently, multifunctional exosomes with tumor-targeted imaging and therapeutic potential have aroused widespread interest in cancer research. Herein, we developed a multifunctional HEK-293T exosome-based targeted delivery platform by engineering HEK-293T cells to express a well-characterized exosomal membrane protein (Lamp2b) fused to the αv integrin-specific iRGD peptide and tyrosine fragments. This platform was loaded with doxorubicin (Dox) and labeled with radioiodine-131 (131I) using the chloramine-T method. iRGD exosomes showed highly efficient targeting and Dox delivery to integrin αvß3-positive anaplastic thyroid carcinoma (ATC) cells as demonstrated by confocal imaging and flow cytometry in vitro and an excellent tumor-targeting capacity confirmed by single-photon emission computed tomography-computed tomography after labeling with 131I in vivo. In addition, intravenous injection of this vehicle delivered Dox and 131I specifically to tumor tissues, leading to significant tumor growth inhibition in an 8505C xenograft mouse model, while showing biosafety and no side effects. These as-developed multifunctional exosomes (denoted as Dox@iRGD-Exos-131I) provide novel insight into the current treatment of ATC and hold great potential for improving therapeutic efficacy against a wide range of integrin αvß3-overexpressing tumors.

Improved Pre-attentive Processing With Occipital rTMS Treatment in Major Depressive Disorder Patients Revealed by MMN.

OBJECTIVES: To investigate the improvement effect of occipital repetitive transcranial magnetic stimulation (rTMS) combined with escitalopram oxalate tablets on pre-attentive processing in patients with first-episode, medication-naive depression. METHODS: Patients who were hospitalized between January and December 2019 were selected. They were randomly allocated to real occipital rTMS stimulation group with 27 cases receiving intermittent theta-burst (iTBS) and sham stimulation group with 24 cases over 20 days. The rTMS treatment target is located at the Oz point of the occipital region. Both groups took escitalopram oxalate tablets, and the average daily drug dose was 15.294 ± 5.041 mg. Hamilton Depression Rating Scale (HAMD) was used to assess the symptoms of depression before and after treatment, and mismatch negativity (MMN) was used to assess the improvement of pre-attentive processing before and after treatment. RESULTS: After 20 days of treatment, the total score of HAMD (13.495 ± 3.700) in both groups was significantly lower than that before treatment [21.910 ± 3.841, F(1, 49) = 46, 3.690, p < 0.001]. After treatment, the latency of MMN in the real stimulation group (182.204 ± 31.878 ms) was significantly lower than that in the sham stimulation group (219.896 ± 42.634 ms, p < 0.001), and the amplitude of MMN in the real stimulation group (-7.107 ± 3.374 ms) was significantly higher than that in the sham stimulation group (-2.773 ± 3.7 32 ms, p < 0.001). CONCLUSION: Occipital rTMS treatment can enhance the early therapeutic effect and effectively improve the pre-attentive processing of patients with depression and provide a scientific basis for the new target of rTMS therapy in clinical patients with depression.

Predictive Value of Thyroglobulin Changes for the Curative Effect of Radioiodine Therapy in Patients With Metastatic Differentiated Thyroid Carcinoma.

Background: Serum thyroglobulin (Tg) serves as a sensitive and easily available tumor marker for patients with metastatic differentiated thyroid carcinoma (m-DTC). The aim of the present study was to evaluate the predictive value of suppressed Tg changes (Δsup-Tg) and/or stimulated Tg changes (Δsti-Tg) to evaluate the efficacy of radioiodine therapy (RT). Methods: We studied 117 patients with m-DTC who received RT. Δsup-Tg and Δsti-Tg were compared after the first RT in different therapeutic response groups and a receiver-operating characteristic (ROC) curve was used to determine the cut-off values to predict non-remission. Univariate and multivariate analyses were used to investigate the effects of 17 observed factors on the efficacy of RT. Results: A total of 218 RT events in 117 patients with m-DTC were analyzed. After the last RT, the remission rate was 70.94% (83/117), and the proportion of remission events accounted for 74.77% (163/218). ROC curve analysis showed that the cut-off values for Δsup-Tg and Δsti-Tg after the first RT to predict the non-remission of RT were 21.54% and 27.63%, respectively. Age, the size of the metastasis, the maximum count of target metastatic lesions and the average count of contralateral non-target tissue on tomographic imaging (Tmax/NTmean) of the first RT, and Δsup-Tg after the first RT were identified as independent factors associated with RT efficacy. Conclusions: Tg response was valuable to predict RT efficacy for patients with m-DTC. Age, the size of the metastasis, Tmax/NTmean, and Δsup-Tg after the first RT were verified as independent predictive factors of RT efficacy.

Predictive Value of a Thyroid-Absorbed Dose with a Shorter Effective Half-Life on Efficacy in Graves Disease Patients Receiving Iodine-131 Therapy.

BACKGROUND Although radioiodine therapy (RIT) efficacy is thoroughly validated for Graves disease (GD), there is a lack of research on the predictive factors of RIT, especially the optimal thyroid-absorbed dose (TD) with a shorter effective half-life (Teff ≤5 days). The goal of this study was to explore the predictive value of TD in GD patients receiving RIT with a shorter Teff. MATERIAL AND METHODS We studied 208 GD patients receiving RIT with a shorter Teff. Plotting the receiver-operating characteristic (ROC) curve verified the accuracy of TD for predicting RIT efficacy in GD patients. In addition, we conducted univariate and multivariate analyses to investigate the influence of 14 factors, including thyroid weight, TD, 24-h radioiodine uptake rate (RAIU), the highest RAIU, thyrotrophin receptor antibody level, thyroglobulin antibody level, thyroid peroxidase antibody level, and others, on curative effects of RIT. RESULTS Of the 208 study participants, complete remission and the total effectiveness rates were 68.3% and 92.3%, respectively. The threshold value of TD to predict RIT efficacy was 70.2 Gy, based on ROC analysis. Univariate analysis showed that 24-h RAIU, Teff, total iodine dose, iodine dose per gram of thyroid tissue, TD, and thyrotropin receptor antibody level were significantly associated with RIT efficacy. Multivariate analysis indicated that 24-h RAIU, total iodine dose, iodine dose per gram of thyroid tissue, and TD were significant independent predictors of RIT efficacy. CONCLUSIONS Predicting RIT efficacy from TD with a shorter Teff was feasible in GD patients, and TD above 70.2 Gy had an especially high predictive accuracy.

Selenium Supplementation May Decrease Thyroid Peroxidase Antibody Titer via Reducing Oxidative Stress in Euthyroid Patients with Autoimmune Thyroiditis.

OBJECTIVE: Selenium, as an antioxidant, has been implicated in the development of autoimmune thyroiditis (AIT). Many studies showed selenium supplementation could decrease thyroid autoantibodies in patients with AIT. However, the underlying mechanisms have not been well determined. Therefore, we performed a clinical study to investigate the possible mechanism of beneficial effects of selenium treatment on AIT patients. METHODS: Forty euthyroid patients with AIT were randomized into two groups. Group I was treated with 200 µg/day selenium supplementation, and group II received a placebo over a 3-month period. Thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), antithyroglobulin antibody (TgAb), malondialdehyde (MDA), total antioxidant capacity (TAC), and superoxide dismutase (SOD) were measured before and 3 months after treatments. Additionally, twenty healthy volunteers also served as a control group for the evaluation of such parameters in basic condition. RESULTS: Totally, 32 patients (group I, n = 18; group II, n = 14) completed the clinical study and were incorporated into the statistics. MDA level was higher and SOD activity and TAC were lower in patients compared to healthy individuals. After 3 months, TPOAb titer significantly decreased within group I (P < 0.001) but did not change within group II (P=0.001). There were also no statistically significant changes in TSH and TgAb titers within the two groups (all P > 0.05). Additionally, decreased MDA level (from 6.8 ± 1.3 nmol/ml to 4.9 ± 0.7 nmol/ml; P < 0.001) and increased TAC (from 10.0 ± 1.9 mmol/l to 12.9 ± 3.1 mmol/l; P=0.003) and SOD activity (from 72.3 ± 10.3 U/ml to 84.3 ± 13.2 U/ml; P=0.007) were simultaneously observed after 3 months' selenium treatment. Moreover, there was a negative correlation between TAC and TgAb/TPOAb and a positive correlation between MDA and TgAb/TPOAb in AIT patients. CONCLUSIONS: Our findings support the hypothesis that selenium treatment could decrease TPOAb titer via enforcing the defense against oxidative stress in euthyroid patients with AIT, which may be a potential underlying mechanism.

Effect of mesoporous silica nanoparticles co­loading with 17­AAG and Torin2 on anaplastic thyroid carcinoma by targeting VEGFR2.

Anaplastic thyroid carcinoma (ATC) is a highly aggressive tumor with a poor prognosis and a low median survival rate because of insufficient effective therapeutic modalities. Recently, mesoporous silica nanoparticles (MSNs) as a green non­toxic and safe nanomaterial have shown advantages to be a drug carrier and to modify the targeting group to the targeted therapy. To aim of the study was to explore the effects of MSNs co­loading with 17­allylamino­17­demethoxy­geldanamycin (17­AAG; HSP90 inhibitor) and 9­(6­aminopyridin­3­yl)­1­(3­(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin­2(1H)­one (Torin2; mTOR inhibitor) by targeting vascular endothelial growth factor receptor 2 (VEGFR2) on the viability of human anaplastic thyroid carcinoma FRO cells. The cytotoxicity of 17­AAG and Torin2 were analyzed by MTT assay. The possible synergistic antitumor effects between 17­AAG and Torin2 were evaluated by CompuSyn software. Flow cytometry was performed to assess the VEGFR2 targeting of (17­AAG+Torin2)@MSNs­anti­VEGFR2 ab and uptake by FRO cells. An ATC xenograft mouse model was established to assess the antitumor effect of (17­AAG+Torin2)@MSNs­anti­VEGFR2 ab in vivo. The results revealed that the combination of 17­AAG and Torin2 inhibited the growth of FRO cells more effectively compared with single use of these agents. Additionally, the synergistic antitumor effect appeared when concentration ratio of the two drugs was 1:1 along with total drug concentration greater than 0.52 µM. Furthermore, in an ATC animal model, it was revealed that the (17­AAG+Torin2)@MSNs­anti­VEGFR2 ab therapy modality could most effectively prolong the median survival time [39.5 days vs. 33.0 days (non­targeted) or 27.5 days (control)]. Compared to (17­AAG+Torin2)@MSNs, the (17­AAG+Torin2)@MSNs­anti­VEGFR2 ab could not only inhibit ATC cell growth but also prolong the median survival time of tumor­bearing mice in vivo and vitro more effectively, which may provide a new promising therapy for ATC.

Antitumor Effect of 131I-Labeled Anti-VEGFR2 Targeted Mesoporous Silica Nanoparticles in Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) comprises approximately 2% of all thyroid cancers, and its median survival rate remains poor because of its resistance to conventional therapy. Vascular endothelial growth factor receptor (VEGFR)-targeted therapeutics-loaded mesoporous silica nanoparticles represent a major advance for angiogenesis imaging and inhibition in lethal cancers. In the present study, we aimed to assess whether 131I-labeled anti-VEGFR2 targeted mesoporous silica nanoparticles would have antitumor efficacy in an ATC tumor-bearing nude mouse model. Using in vitro and in vivo studies, we investigated the increased targeting ability and retention time in the anti-VEGFR2 targeted group using confocal microscopy and a γ counter. The tumor tissue radioactivity of the anti-VEGFR2 targeted group at 24 and 72 h after intratumoral injection was significantly higher than that of the non-targeted groups (all P < 0.05). Moreover, we found that radioactive accumulation was obvious even at 3 week post-injection in the anti-VEGFR2 targeted group via single-photon emission computed tomography/computed tomography, which was not seen at 3 day post-injection in the Na131I group. Meanwhile, compared with the non-targeted group, tumor growth in the targeted group was significantly inhibited, without causing apparent systemic toxic effects. Additionally, the median survival time in the targeted group (41 days) was significantly prolonged compared with that in the non-targeted (34 days) or Na131I (25 days) groups (both P < 0.01). Our data support the view that the as-developed 131I-labeled anti-VEGFR2 targeted mesoporous silica nanoparticles showed promising results in ATC tumor-bearing mouse model and such an approach might represent a novel therapeutic option for ATC.

Multiple Heterotopic Ossification of the Intestine Detected by 99mTc-MDP Bone Scan in a Patient With Primary Peritoneal Cancer.

Heterotopic ossification is a rare phenomenon that refers to formation of bone outside the skeletal system. We present a 61-year-old woman who suffered from peritoneal cancer surgery 2 years ago, referred for Tc-MDP bone scan because of higher serum CA-125 level, which showed multiple intense tracer activities in her abdominal and pelvic region without other abnormalities. SPECT/CT revealed the activities were loaded in the intestine but not in the bone. A wait-and-see policy was adopted because of no abdominal discomfort. After 1-year follow-up, another bone scintigraphy showed the tracer uptake was significantly decreased.

A Case of Fronto-Temporal Dementia (FTD) Masquerading as Mood Disorder.

A 56-year old Chinese female was referred to an academic medical center with atypical, treatment-resistant depression that continued for approximately 3 years after her sister's death. Comprehensive evaluation including neurocognitive testing, EEG, spinal tap, HIV testing and brain MRI revealed behavioral variant of fronto-temporal dementia (bvFTD) with significant frontal and temporal lobe atrophy.This patient's unusual clinical presentation emphasizes the overlap between depression and bvFTD, and underlines the importance of prompt, accurate diagnosis to minimize often-ineffective pharmacological interventions and caregiver burnout.