Application of catalytic technology based on the piezoelectric effect in wastewater purification.

The demands of human life and industrial activities result in a significant influx of toxic contaminants into aquatic ecosystems. In particular, organic pollutants such as antibiotics and dye molecules, bacteria, and heavy metal ions are represented, posing a severe risk to the health and continued existence of living organisms. The method of removing pollutants from water bodies by utilizing the principle of the piezoelectric effect in combination with chemical catalytic processes is superior to other wastewater purification technologies because it can collect water energy, mechanical energy, etc. to achieve cleanliness and high removal efficiency. Herein, we briefly introduced the piezoelectric mechanisms and then reviewed the latest advances in the design and synthesis of piezoelectric materials, followed by a summary of applications based on the principle of piezoelectric effect to degrade pollutants in water for wastewater purification. Moreover, water purification technologies incorporating the piezoelectric effect, including piezoelectric effect-assisted membrane filtration, activation of persulfate, and battery electrocatalysis are elaborated. Finally, future challenges and research directions for the piezoelectric effect are proposed.

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) patient with ARMC5 mutations.

BACKGROUND: Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a highly heterogeneous disease with divergent manifestations ranging from asymptomatic subclinical Cushing syndrome (CS) to overt Cushing syndrome with severe complications. ARMC5 mutations occur in 20 to 55% PBMAH patients usually with more severe phenotypes. Different ARMC5 mutations might be associated with diverse phenotypes of PBMAH. CASE PRESENTATION: A 39-year-old man was admitted to our hospital with progressive weight gain and severe hypertension. He presented typical CS and its classical metabolic and bone complications like hypertension and osteoporosis. The laboratory results showed high levels of cortisol and low levels of ACTH. Low- and high-dosed dexamethasone suppression tests were negative. Contrast-enhanced computed tomography (CT) revealed multiple bilateral irregular macronodular adrenal masses. Adrenal venous sampling (AVS) confirmed that the right adrenal gland with larger nodules secreted more hormone that the left side did. Right adrenalectomy and subsequent contralateral subtotal resection were conducted. His blood pressure and CS symptoms as well as comorbidities including backache and muscle weakness improved. Whole exome sequencing identified one ARMC5 germline mutation (c.1855C > T, p. R619*), five ARMC5 somatic mutations (four novel mutations) in his right and left adrenal nodules. CONCLUSIONS: This PBMAH patient was identified with one ARMC5 germline mutation and five different somatic ARMC5 mutations (four novel mutations) in the different nodules of the bilateral adrenal masses. AVS combined with CT imagine could be helpful to determine the dominant side for adrenalectomy. Genetic testing is important for the diagnosis and management of the patient with PBMAH.

Genome Sequencing Highlights the Plant Cell Wall Degrading Capacity of Edible Mushroom Stropharia rugosoannulata.

The basidiomycetous edible mushroom Stropharia rugosoannulata has excellent nutrition, medicine, bioremediation, and biocontrol properties. S. rugosoannulata has been widely and easily cultivated using agricultural by-products showing strong lignocellulose degradation capacity. However, the unavailable high-quality genome information has hindered the research on gene function and molecular breeding of S. rugosoannulata. This study provided a high-quality genome assembly and annotation from S. rugosoannulata monokaryotic strain QGU27 based on combined Illumina-Nanopore data. The genome size was about 47.97 Mb and consisted of 20 scaffolds, with an N50 of 3.73 Mb and a GC content of 47.9%. The repetitive sequences accounted for 17.41% of the genome, mostly long terminal repeats (LTRs). A total of 15,726 coding gene sequences were putatively identified with the BUSCO score of 98.7%. There are 142 genes encoding plant cell wall degrading enzymes (PCWDEs) in the genome, and 52, 39, 30, 11, 8, and 2 genes related to lignin, cellulose, hemicellulose, pectin, chitin, and cutin degradation, respectively. Comparative genomic analysis revealed that S. rugosoannulata is superior in utilizing aldehyde-containing lignins and is possible to utilize algae during the cultivation.

Neoadjuvant Chemotherapy Improves the Immunosuppressive Microenvironment of Bladder Cancer and Increases the Sensitivity to Immune Checkpoint Blockade.

Although tumor immune microenvironment plays an important role in antitumor therapy, few studies explored the gene signatures associated with the tumor immune microenvironment of bladder cancer after neoadjuvant chemotherapy. We examined and analyzed differentially expressed genes from 9 patients with stage I-III bladder cancer by RNA immune-oncology profiling platform. After neoadjuvant chemotherapy, the expressions of 43 genes in 19 pathways and 10 genes in 5 pathways were upregulated and downregulated, respectively. Neoadjuvant chemotherapy also promoted the expression of genes related to the activation of antitumor immune responses and decreased the expression of genes related to tumor proliferation pathways. In addition, neoadjuvant chemotherapy improved tumor response to immune checkpoint blockade. Furthermore, this study also identified several genes that can be used to predict the efficacy of neoadjuvant chemotherapy and their possible molecular mechanisms. In conclusion, neoadjuvant chemotherapy may promote the activation of antitumor effects, improve the suppressive tumor immune microenvironment, and increase the sensitivity of bladder cancer to immune checkpoint blockade.

Population genomics provides insights into the genetic basis of adaptive evolution in the mushroom-forming fungus Lentinula edodes.

Introduction: Mushroom-forming fungi comprise diverse species that develop complex multicellular structures. In cultivated species, both ecological adaptation and artificial selection have driven genome evolution. However, little is known about the connections among genotype, phenotype and adaptation in mushroom-forming fungi. Objectives: This study aimed to (1) uncover the population structure and demographic history of Lentinula edodes, (2) dissect the genetic basis of adaptive evolution in L. edodes, and (3) determine if genes related to fruiting body development are involved in adaptive evolution. Methods: We analyzed genomes and fruiting body-related traits (FBRTs) in 133 L. edodes strains and conducted RNA-seq analysis of fruiting body development in the YS69 strain. Combined methods of genomic scan for divergence, genome-wide association studies (GWAS), and RNA-seq were used to dissect the genetic basis of adaptive evolution. Results: We detected three distinct subgroups of L. edodes via single nucleotide polymorphisms, which showed robust phenotypic and temperature response differentiation and correlation with geographical distribution. Demographic history inference suggests that the subgroups diverged 36,871 generations ago. Moreover, L. edodes cultivars in China may have originated from the vicinity of Northeast China. A total of 942 genes were found to be related to genetic divergence by genomic scan, and 719 genes were identified to be candidates underlying FBRTs by GWAS. Integrating results of genomic scan and GWAS, 80 genes were detected to be related to phenotypic differentiation. A total of 364 genes related to fruiting body development were involved in genetic divergence and phenotypic differentiation. Conclusion: Adaptation to the local environment, especially temperature, triggered genetic divergence and phenotypic differentiation of L. edodes. A general model for genetic divergence and phenotypic differentiation during adaptive evolution in L. edodes, which involves in signal perception and transduction, transcriptional regulation, and fruiting body morphogenesis, was also integrated here.

Microscopic Replantation of Complete Penile Amputation With Video Demonstration.

BACKGROUND: Penile amputation is an extremely rare genital injury. To the best of our knowledge, there are only about 200 cases reported in Chinese and English literature, most of them are case reports. So far, there is not any video demonstration of microscopic replantation of complete penile amputation with meticulous surgical skills. OBJECTIVE: To provide a successful example of penile replantation after complete penile amputation through video presentation of the application of meticulous microsurgical techniques and optimized procedures. MATERIALS AND METHODS: The 25-year-old patient was admitted to our hospital 3.5 hours after his penis was completely amputated due to self-mutilation. Microscopic penile replantation was immediately performed after preoperative preparation. After the surgical procedure, the patient was treated with broad-spectrum antibiotics, analgesia, antithrombotics and anxiolytic. RESULTS: The total ischemic time was about 10 hours. The duration of surgery was about 7 hours. On the 14th day post-surgery, the wound healed smoothly, the glans was ruddy in color, and the appearance returned to normal without obvious complications. The patient urinates normally with a maximal urinary flow rate of 25 ml/s after removing the catheter. Three months after surgery, the local sensation of foreskin and glans recovered significantly, which showed that slight needling could lead to obvious pain, and the penis erection hardness score was 3 during morning erection or urinary bladder distention. Six months after surgery, the patient reported that he was completely satisfied with the result, which showed that the sensation of the penis and glans surface returned to almost normal and the optimal erection hardness score was 4. CONCLUSION: Careful microsurgical anastomosis of the dorsal arteries, deep dorsal vein, superficial dorsal vein and multiple dorsal nerves could obtain ideal recovery of penile appearance and function and avoid any obvious complications.

Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2.

Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration-resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without Phf8 failed to develop NEPC. Mechanistically, PHF8 transcriptionally upregulates FOXA2 by demethylating and removing the repressive histone markers on the promoter region of the FOXA2 gene, and the upregulated FOXA2 subsequently regulates the expression of genes involved in NEPC development. Since both PHF8 and FOXA2 are highly expressed in NEPC tissues from patients or patient-derived xenografts, the levels of PHF8 and FOXA2 can either individually or in combination serve as NEPC biomarkers and targeting either PHF8 or FOXA2 could be potential therapeutic strategies for NEPC treatment. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Case Report: Co-Existence of BRCA2 and PALB2 Germline Mutations in Familial Prostate Cancer With Solitary Lung Metastasis.

BACKGROUND: Mutation-caused loss-of-function of factors involved in DNA damage response (DDR) is responsible for the development and progression of ~20% of prostate cancer (PCa). Some mutations can be used in cancer risk assessment and informed treatment decisions. METHODS: Target capture-based deep sequencing of 11 genes was conducted with total DNA purified from the proband's peripheral blood. Sanger sequencing was conducted to screen potential germline mutations in the proband's family members. Targeted sequencing of a panel of 1,021 genes was done with DNA purified from the tumor tissue. RESULTS: Two previously unreported germline mutations in the DDR pathway, BRCA2 (c.8474_8487delCATACCCTATACAG, p.A2825Vfs*15) and PALB2 (c.472delC, p.Q158Rfs*19) were identified in a patient with metastatic PCa. A specific therapeutic regimen including androgen deprivation therapy, locally radical radiotherapy, and systemic platinum chemotherapy worked well against his cancer. In addition, the metastatic ovarian cancer in the proband's half-sister harboring the same BRCA2 germline mutation also responded well to platinum chemotherapy. CONCLUSIONS: The newly identified germline mutations in DDR plays important role in PCa development. Since specific regimen worked well against this cancer, screening of DDR mutation could provide better management for patients with these mutation-mediated PCa.

LSD1 Promotes Bladder Cancer Progression by Upregulating LEF1 and Enhancing EMT.

Epithelial-to-mesenchymal transition (EMT) is one of the important underlying molecular mechanisms for most types of cancers including bladder cancer. The precise underlying molecular mechanism in EMT-mediated bladder cancer progression is far from completed. LSD1, a histone lysine-specific demethylase, is known to promote cancer cell proliferation, metastasis, and chemoresistance. We found in this study that LSD1 is highly upregulated in bladder cancer specimens, especially those underwent chemotherapy, and the elevated levels of LSD1 are highly associated with bladder cancer grades, metastasis status, and prognosis. Inhibiting or knockdown LSD1 repressed not only EMT process but also cancer progression. Mechanistically, LSD1 complexes with ß-catenin to transcriptionally upregulate LEF1 and subsequently enhances EMT-mediated cancer progression. More importantly, LSD1 specific inhibitor GSK2879552 is capable of repressing tumor progression in patient-derived tumor xenograft. These findings altogether suggest that LSD1 can serve as not only a prognostic biomarker but also a promising therapeutic target in bladder cancer treatment.

A Renal Cell Carcinoma with Biallelic Somatic TSC2 Mutation: Clinical Study and Literature Review.

OBJECTIVE: To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC). METHODS: Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted. RESULTS: Two novel somatic mutations of TSC2 in unilateral and solitary RCC samples from a 14-year-old female were identified. The pathological features suggest the tumor as a clear-cell renal cell carcinoma. In addition, immunohistochemistry revealed elevated levels of phosphorylated S6K1. Results from in vitro cellular experiments suggest that the mutant TSC2 proteins were quickly degraded and they failed to repress the phosphorylation of S6K1 and STAT3, which leads to constitutive activation of mTORC1 pathway and ultimately cause the development of RCC. CONCLUSION: Detecting TSC2 mutation in patients with early RCC onset would be beneficial and mTOR inhibitor could be a therapeutic option for TSC2 mutation-induced RCC.

Giant bilateral adrenal myelolipomas in two Chinese families with congenital adrenal hyperplasia.

CONTEXT AND OBJECTIVES: Congenital adrenal hyperplasia (CAH) is one of the most prevalent, and potentially severe, genetic inborn errors of steroid synthesis directly affecting metabolism. Most patients are diagnosed and treated at an early age. There have been very limited reports of adults with CAH-associated adrenal myelolipomas. We aimed to analyze two families with CAH-associated giant adrenal myelolipomas caused by defects in CYP21A2 and CYP17A1 genes. PARTICIPANTS AND METHODS: A total of 14 individuals from two unrelated families were identified with either CYP21A2 or CYP17A1 mutations. Of note, 5 patients were found with adrenal myelolipomas. Total DNA isolated from the peripheral blood of the two probands was screened for potential mutations in the following susceptibility genes of CAH: CYP21A2, CYP11B1, CYP17A1, HSD17B3, HSD3B2, ARMC5, and STAR using Target Capture-Based Deep Sequencing; and Sanger sequencing was conducted for the family members to detect the potential mutations. RESULTS: In family 1, molecular genetics sequencing revealed a compound heterozygous mutation (c.293-13C>G / c.518T>A, p.I173N) in CYP12A2 in the patient and his brother. In family 2, all three female patients with adrenal myelolipomas were found to have a compound heterozygous mutation (c.1118A>T, p.H373L / c.1459_1467del9, p.D487_F489del) in CYP17A1. CONCLUSION: To avoid giant CAH-associated adrenal myelolipomas in adults, it is important to identify CAH early so appropriate treatment can be initiated to interrupt the chronic adrenal hyperstimulation resulting from increased ACTH. Genetic testing and counseling could be useful in CAH.

The roles of the COX2/PGE2/EP axis in therapeutic resistance.

Therapeutic resistance has been and remains to be the major challenge in developing successful treatments for different cancers and therefore, understanding the underlying mechanisms in the development of therapeutic resistance is crucial in combating cancers. Multiple mechanisms underlie the development of therapeutic resistance, and the signaling pathways involved in cancer stem cell repopulation, enhanced epithelial-mesenchymal transition (EMT), inflammatory infiltration, and immunosuppression play pivotal roles in this process. Accumulating evidence indicates that the COX2/PGE2/EP axis plays crucial roles not only in tumor development including initiation and progression but also in the development of therapeutic resistance. In this review, we will first dissect the relationship between the COX2/PGE2/EP axis and therapeutic resistance by focusing on the roles of the COX2/PGE2/EP axis in cancer stem cell repopulation, EMT, and anti-cancer immunity. Then, we will summarize the currently available compounds/drugs targeting each component of this axis as well as some of the underlying mechanisms. We hope that better understanding the underlying mechanisms of the functional compounds will be helpful in seeking additive and/or synergistic effects against therapeutic resistance without or with minimal adverse consequence.

Metformin Inhibits Prostate Cancer Progression by Targeting Tumor-Associated Inflammatory Infiltration.

Purpose: Inflammatory infiltration plays important roles in both carcinogenesis and metastasis. We are interested in understanding the inhibitory mechanism of metformin on tumor-associated inflammation in prostate cancer.Experimental Design: By using a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, in vitro macrophage migration assays, and patient samples, we examined the effect of metformin on tumor-associated inflammation during the initiation and after androgen deprivation therapy of prostate cancer.Results: Treating TRAMP mice with metformin delays prostate cancer progression from low-grade prostatic intraepithelial neoplasia to high-grade PIN, undifferentiated to well-differentiated, and PIN to adenocarcinoma with concurrent inhibition of inflammatory infiltration evidenced by reduced recruitment of macrophages. Furthermore, metformin is capable of inhibiting the following processes: inflammatory infiltration after androgen deprivation therapy (ADT) induced by surgically castration in mice, bicalutamide treatment in patients, and hormone deprivation in LNCaP cells. Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells.Conclusions: Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting the COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment. Clin Cancer Res; 24(22); 5622-34. ©2018 AACR.

A retrospective case study of sunitinib treatment in three patients with Von Hippel-Lindau disease.

Von Hippel-Landau (VHL) disease is characterized by malignant and benign tumors in multiple organs. Sunitinib, a tyrosine kinase inhibitor, has been clinically available for treating sporadic patients with recurrent or unresectable and metastatic clear renal cell carcinomas (cRCCs) and metastatic lesions of the lung, but its effect on VHL disease-associated tumors remains poorly understood. This retrospective case series examined the effect of sunitinib on RCC, hemangioblastomas, pheochromocytomas, and pancreatic neuroendocrine tumors in patients with confirmed VHL. Of note, three patients with VHL disease who were treated with sunitinib were identified from a review of their medical records. The efficacy of sunitinib was evaluated by comparing computed tomography (CT) or magnetic resonance imaging (MRI) scans conducted before and after treatment. Adverse side effects associated with sunitinib were assessed and recorded. All three patients with VHL disease exhibited clinical improvement after treatment with sunitinib. Patient 1 exhibited a decrease in the size of both their pheochromocytoma and RCC after 19 months of sunitinib treatment. RCCs in Patients 2 and 3 exhibited stable response to sunitinib for approximately 1 and 6 years, respectively. All the patients reported tolerable side effects. Therefore sunitinib treatment was associated with either partial response or stable control of VHL-related RCCs, pheochromocytomas and pancreatic neuroendocrine tumor (NET) with acceptable side effects. Further evaluation of sunitinib in patients with VHL disease in larger prospective studies is warranted.

Novel genotype-phenotype correlations in five Chinese families with Von Hippel-Lindau disease.

CONTEXT: Von Hippel-Lindau (VHL) disease manifests as a variety of benign and malignant neoplasms. Previous studies of VHL disease have documented several genotype-phenotype correlations; however, many such correlations are still unknown. Increased identification of new mutations and patients with previously described mutations will allow us to better understand how VHL mutations influence disease phenotypes. PATIENTS AND DESIGN: A total of 45 individuals from five unrelated families were evaluated, of which 21 patients were either diagnosed with VHL disease or showed strong evidence related to this disease. We compared the patients' gene sequencing results with their medical records including CT or MRI scans, eye examinations and laboratory/pathological examinations. Patients were also interviewed to obtain information regarding their family history. RESULTS: We identified four missense mutations: c.239G>T (p.Ser80Ile), linked with VHL Type 2B, was associated with renal cell carcinoma, pheochromocytoma and hemangioma in the cerebellum; c.232A>T (p.Asn78Tyr) manifested as RCC alone and likely caused VHL Type 1; c.500G>A (p.Arg167Gln) mutation was more likely to cause VHL Type 2 than Type 1 as it preferentially induced Pheo and HB in the retina, cerebellum and spinal cord; c.293A>G (p.Try98Cys) was associated with Pheo and thus likely induced VHL Type 2. CONCLUSIONS: Characterizing VHL disease genotype-phenotype correlations can enhance the ability to predict the risk of individual patients developing different VHL-related phenotypes. Ultimately, such insight will improve the diagnostics, surveillance and treatment of VHL patients. PRECIS: Four missense mutations in VHL have been identified in 21 individuals when five unrelated Chinese families with VHL disease were analyzed; VHL mutations are highly associated with unique disease phenotypes.

A novel BRCA2 mutation in prostate cancer sensitive to combined radiotherapy and androgen deprivation therapy.

Genetic factors contribute to more than 40% of prostate cancer risk, and mutations in BRCA1 and BRCA2 are well-established risk factors. By using target capture-based deep sequencing to identify potential pathogenic germline mutations, followed by Sanger sequencing to determine the loci of the mutations, we identified a novel pathogenic BRCA2 mutation caused by a cytosine-to-guanine base substitution at position 4211, resulting in protein truncation (p.Ser1404Ter), which was confirmed by immunohistochemistry. Analysis of peripheral blood also identified benign polymorphisms in BRCA2 (c.7397T>C, p.Val2466Ala) and SRD5A2 (c.87G>C, p.Lys29Asn). Analysis of tumor tissues revealed seven somatic mutations in prostate tumor tissue and nine somatic mutations in esophageal squamous carcinoma tissue (single nucleotide polymorphisms, insertions, and deletions). Five-year follow-up results indicate that ADT combined with radiotherapy successfully treated the prostate cancer. To our knowledge, we are the first to report the germline BRCA2 mutation c.4211C>G (p.Ser1404Ter) in prostate cancer. Combined ADT and radiotherapy may be effective in treating other patients with prostate cancer caused by this or similar mutations.

HIF2A germline-mutation-induced polycythemia in a patient with VHL-associated renal-cell carcinoma.

In this study, we report here a rare case of polycythemia and cRCC in the same patient, which may be helpful in understanding clinical features and molecular mechanisms underlying VHL-mutation-associated cRCC and polycythemia induced by germline mutation of HIF2A. Firstly, we identified a rare but well studied germline mutation resulting in polycythemia in HIF2A (c.1609G>A, p.Gly537Arg) in the blood of the patient and his daughter. Meanwhile, we identified an inactivating VHL mutation (c.391A>T, p.N131Y), as well as TP53 mutation(c.977A>T, p.E326V) and mTOR mutation(c.7498A>T, p.I2500F) in renal cancer tissue. Moreover, protein levels of VHL, HIF1A, HIF2A, EPO, and VEGF estimated by immunohistochemical staining substantiated hyperactivation of the oxygen-sensing pathway. In addition, we identified 158 somatic SNP/indel mutations, including 90 missense/nonsense/splice/stop-loss mutations by whole-exome sequencing (WES) of the tumor specimen and matched normal DNA.

Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-ß1/STAT3 axis-regulated EMT.

Although the newly developed second-generation anti-androgen drug enzalutamide can repress prostate cancer progression significantly, it only extends the survival of prostate cancer patients by 4-6 months mainly due to the occurrence of enzalutamide resistance. Most of the previous studies on AR antagonist resistance have been focused on AR signaling. Therefore, the non-AR pathways on enzalutamide resistance remain largely unknown. By using C4-2, CWR22Rv1 and LNCaP cell lines, as well as mice bearing CWR22Rv1 xenografts treated with either enzalutamide or metformin alone or in combination, we demonstrated that metformin is capable of reversing enzalutamide resistance and restores sensitivity of CWR22Rv1 xenografts to enzalutamide. We showed that metformin alleviated resistance to enzalutamide by inhibiting EMT. Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-ß1, we propose that metformin exerts its effects by targeting the TGF-ß1/STAT3 axis. These findings suggest that combination of metformin with enzalutamide could be a more efficacious therapeutic strategy for the treatment of castration-resistant prostate cancer.

Different RET gene mutation-induced multiple endocrine neoplasia type 2A in 3 Chinese families.

BACKGROUD: Multiple endocrine neoplasia type 2A (MEN2A) is a condition with inherited autosomal dominant mutations in RET (rearranged during transfection) gene that predisposes the carrier to extremely high risk of medullary thyroid cancer (MTC) and other MEN2A-associated tumors such as parathyroid cancer and/or pheochromocytoma. Little is reported about MEN2A syndrome in the Chinese population. METHODS: All members of the 3 families along with specific probands of MEN2A were analyzed for their clinical, laboratory, and genetic characteristics. Exome sequencing was performed on the 3 probands, and specific mutation in RET was further screened on each of the family members. RESULTS: Different mutations in the RET gene were identified: C634S in Family 1, C611Y in Family 2, and C634Y in Family 3. Proband 1 mainly showed pheochromocytoma with MTC, both medullary thyroid carcinoma and pheochromocytoma were seen in proband 2, and proband 3 showed medullary thyroid carcinoma. CONCLUSION: The genetic evaluation is strongly recommended for patients with a positive family history, early onset of age, or multiple sites of masses. If the results verified the mutations of RET gene, thyroidectomy should be undertaken as the guide for better prognosis.

Metformin inhibits castration-induced EMT in prostate cancer by repressing COX2/PGE2/STAT3 axis.

Castration is the standard therapeutic treatment for advanced prostate cancer but with limited benefit due to the profound relapse and metastasis. Activation of inflammatory signaling pathway and initiation of epithelial-mesenchymal transition (EMT) are closely related to drug resistance, tumor relapseas well as metastasis. In this study, we demonstrated that metformin is capable of inhibiting prostate cancer cell migration and invasion by repressing EMT evidenced by downregulating the mesenchymal markers N-cadherin, Vimentin, and Twist and upregulating the epithelium E-cadherin. These effects have also been observed in our animal model as well as prostate cancer patients. In addition, we showed the effects of metformin on the expression of genes involved in EMT through repressing the levels of COX2, PGE2 and phosphorylated STAT3. Furthermore, inactivating COX2 abolishes metformin's regulatory effects and exogenously administered PGE2 is capable of enhancing STAT3 phosphorylation and expression of EMT biomarker. We propose that metformin represses prostate cancer EMT and metastasis through targeting the COX2/PGE2/STAT3 axis. These findings suggest that metformin by itself or in combination with other anticancer drugs could be used as an anti-metastasis therapy.