Clinical observation using virtual reality for dental education on surgical tooth extraction: A comparative study.

BACKGROUND: Clinical observation conducted during the 3rd and 4th years of dental school is an important part of dental students' clinical education. However, conventional clinical observation is associated with several problems, including the lack of opportunity for all students to assist during surgery. Virtual reality (VR) technologies and devices can be used to demonstrate clinical processes that dental students need to learn through clinical observation. This study aimed to evaluate the effectiveness of teaching dental students the surgical tooth extraction procedure through clinical observation using VR. METHODS: We recruited third- and fourth-year dental students and divided them into a VR clinical observation group (VR group) and a conventional clinical observation group (control group). The control group visited an outpatient clinic and observed an oral and maxillofacial specialist perform surgical tooth extraction, whereas the VR group watched a 360° video of surgical tooth extraction using a head-mounted display. After observation, both groups were surveyed regarding their satisfaction with the clinical observation and their understanding of the procedure. RESULTS: Understanding of the procedure and satisfaction with the observation were significantly higher in the VR group than in the control group (p = 0.001 and p = 0.047, respectively). Compared with conventional clinical observation, VR clinical observation improved learning motivation and medical thinking and judgment skills; however, interaction between professors and students was lacking. CONCLUSIONS: VR clinical observation using 360° videos might be an effective teaching method for students. However, to allow interaction between professors and students during clinical observations, using it along with conventional clinical observation is necessary.

The assessment of halitosis with a new screening tool in medication-related osteonecrosis of the jaw.

OBJECTIVES: This study aimed to identify the levels of halitosis in patients with Medication-related osteonecrosis of the jaw (MRONJ) and osteoporosis and to suggest a new MRONJ screening method using halitosis measurement. MATERIALS AND METHODS: From October 2019 to April 2023, participants aged 19 years or older without periodontal disease were selected. Seventy-five participants, 25 in each group, were divided into an MRONJ group, an osteoporosis group without MRONJ, and a control group without osteoporosis and not taking osteoporosis drugs or antibiotics. Each participant underwent halitosis assessment twice using an exhaled breath analyzer to measure halitosis twice by blowing a straw for 1 min. Measured concentrations of hydrogen, hydrogen sulfide, and methyl mercaptan were compared between groups. RESULTS: Data from 22 patients in the MRONJ group, 25 in the osteoporosis group, and 25 in the control group were analyzed. The concentrations of hydrogen sulfide and methyl mercaptan were significantly higher in the MRONJ group than in the other groups, but the concentrations of hydrogen did not differ between the groups. When comparing the concentrations of hydrogen sulfide and methyl mercaptan in osteoporosis patients and solid cancer patients in the MRONJ group, there was a significant difference in hydrogen sulfide concentration, but there was no significant difference in methyl mercaptan. CONCLUSIONS: Quantifying the level of halitosis can be used to screen for MRONJ in patients taking bisphosphonates, such as patients with osteoporosis, prostate cancer, and breast cancer. CLINICAL RELEVANCE: MRONJ is accompanied by bad breath, and the concentrations of hydrogen sulfide and methyl mercaptan are associated with MRONJ.

Beyond Dollars and Scars: The Influence of Wealth Inequality on Total Expenditure on Cosmetic Procedures in the United States.

The present study delves into the "beauty paradox," a multifaceted phenomenon influenced by wealth inequality, societal norms, and consumer behaviors, specifically regarding spending on cosmetic procedures. Relying on data from the United States Census Bureau and the American Society of Plastic Surgeons, the research primarily focuses on the Gini coefficient, Mean Logarithmic Deviation (MLD), and income data for the lowest and top 5% quintiles of mean household income over a 15-year span. The analysis uncovers a significant correlation between Total Expenditures on Cosmetic Surgery and minimally invasive procedures and the wealth of the top 5% income quintile. The "Cosmetic Enhancement Cycle (CEC)" is proposed, indicating a symbiotic growth between wealth accumulation among the affluent and the plastic surgery industry. As such, the "beauty paradox" lays bare the multifaceted consequences of wealth inequality, necessitating a comprehensive approach that addresses socioeconomic dynamics, accessibility of cosmetic procedures, societal norms, and perceptions. This investigation underscores the imperative for further exploration into the myriad ways that wealth inequality sculpts societies and influences behaviors, including within the context of the CEC.

Forced eruption in impacted teeth: analysis of failed cases and outcome of re-operation.

BACKGROUND: Forced eruption of an impacted tooth usually requires surgical and orthodontic interventions to successfully bring the tooth into the dental arch. The clinical time required for a forced eruption is difficult to predict before treatment begins and success rates are affected by several factors before and after an eruption. This study was conducted to identify factors that affect the success of forced eruption, the duration of orthodontic treatment of impacted teeth, and the reasons for re-operation and forced eruption failure in a various teeth and cases. METHODS: In this retrospective study, the records regarding the forced eruption of 468 teeth in 371 patients from June 2006 to May 2020 at the Advanced General Dentistry Department of Yonsei University Dental Hospital were initially examined. The records of 214 teeth in 178 patients who completed orthodontic treatment were included in the analysis. Data on patient demographics, tooth characteristics, orthodontic treatment duration, re-operations, and failures were collected from electronic medical records. RESULTS: There was a significant difference in age between the success and failure forced eruption. Factors significantly affecting treatment duration were apex formation, position, rotation, and re-operation. Re-operation had a 96% success rate. The average orthodontic treatment duration was 29.99 ± 16.93 months, but the average orthodontic treatment duration for teeth that undergone re-operation was 20.36 ± 11.05 months, which was approximately 9 months shorter. Additionally, there was an interaction effect between rotation and re-operation on the duration of orthodontic treatment. The causes for failure of forced eruption in 6 cases were ankyloses (3 cases), incomplete alignment with the normal dental arch (2 cases), and a significant deviation in the impacted tooth's location (1 case). CONCLUSIONS: To increase the success rate of forced eruption, age should be considered as a priority, and in order to predict the treatment period, the apex formation status, position in the arch, and rotation should be considered in addition to age. When determining re-operation, considering factors such as ankylosis, root curvature, and apex formation can help in the success of orthodontic treatment.

Machine Learning Reveals Lipidome Remodeling Dynamics in a Mouse Model of Ovarian Cancer.

Ovarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. In contrast, later stages featured more diverse lipid alterations, including fatty acids and their derivatives, triglycerides, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, and phosphatidylinositols. These alterations underscored unique perturbations in cell membrane stability, proliferation, and survival during cancer development and progression, offering potential targets for early detection and prognosis of human ovarian cancer.

Mechanistically Weighted Metric to Predict In Vivo Antibody-Receptor Occupancy: An Analytical Approach.

In situ clinical measurement of receptor occupancy (RO) is challenging, particularly for solid tumors, necessitating the use of mathematical models that predict tumor receptor occupancy to guide dose decisions. A potency metric, average free tissue target to initial target ratio (AFTIR), was previously described based on a mechanistic compartmental model and is informative for near-saturating dose regimens. However, the metric fails at clinically relevant subsaturating antibody doses, as compartmental models cannot capture the spatial heterogeneity of distribution faced by some antibodies in solid tumors. Here we employ a partial differential equation (PDE) Krogh cylinder model to simulate spatiotemporal receptor occupancy and derive an analytical solution, a mechanistically weighted global AFTIR, that can better predict receptor occupancy regardless of dosing regimen. In addition to the four key parameters previously identified, a fifth key parameter, the absolute receptor density (targets/cell), is incorporated into the mechanistic AFTIR metric. Receptor density can influence equilibrium intratumoral drug concentration relative to whether the dose is saturating or not, thereby influencing the tumor penetration depth of the antibody. We derive mechanistic RO predictions based on distinct patterns of antibody tumor penetration, presented as a global AFTIR metric guided by a Thiele Modulus and a local saturation potential (drug equivalent of binding potential for positron emissions tomography imaging) and validate the results using rigorous global and local sensitivity analysis. This generalized AFTIR serves as a more accurate analytical metric to aid clinical dose decisions and rational design of antibody-based therapeutics without the need for extensive PDE simulations. SIGNIFICANCE STATEMENT: Determining antibody-receptor occupancy (RO) is critical for dosing decisions in pharmaceutical development, but direct clinical measurement of RO is often challenging and invasive, particularly for solid tumors. Significant efforts have been made to develop mathematical models and simplified analytical metrics of RO, but these often require complex computer simulations. Here we present a mathematically rigorous but simplified analytical model to accurately predict RO across a range of affinities, doses, drug, and tumor properties.

A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development.

Exposure-response (E-R) analyses are an integral component in the development of oncology products. Characterizing the relationship between drug exposure metrics and response allows the sponsor to use modeling and simulation to address both internal and external drug development questions (e.g., optimal dose, frequency of administration, dose adjustments for special populations). This white paper is the output of an industry-government collaboration among scientists with broad experience in E-R modeling as part of regulatory submissions. The goal of this white paper is to provide guidance on what the preferred methods for E-R analysis in oncology clinical drug development are and what metrics of exposure should be considered.

Targeting progesterone signaling prevents metastatic ovarian cancer.

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

In vivo modeling of metastatic human high-grade serous ovarian cancer in mice.

Metastasis is responsible for 90% of human cancer mortality, yet it remains a challenge to model human cancer metastasis in vivo. Here we describe mouse models of high-grade serous ovarian cancer, also known as high-grade serous carcinoma (HGSC), the most common and deadliest human ovarian cancer type. Mice genetically engineered to harbor Dicer1 and Pten inactivation and mutant p53 robustly replicate the peritoneal metastases of human HGSC with complete penetrance. Arising from the fallopian tube, tumors spread to the ovary and metastasize throughout the pelvic and peritoneal cavities, invariably inducing hemorrhagic ascites. Widespread and abundant peritoneal metastases ultimately cause mouse deaths (100%). Besides the phenotypic and histopathological similarities, mouse HGSCs also display marked chromosomal instability, impaired DNA repair, and chemosensitivity. Faithfully recapitulating the clinical metastases as well as molecular and genomic features of human HGSC, this murine model will be valuable for elucidating the mechanisms underlying the development and progression of metastatic ovarian cancer and also for evaluating potential therapies.

Developing and Establishing a Wound Dressing Team: Experience and Recommendations.

BACKGROUND: The existing literature has comprehensively examined the benefits of specialized wound-care services and multidisciplinary team care. However, information on the development and integration of wound-dressing teams for patients who do not require specialized wound care is scarce. Therefore, the present study aimed to elucidate the benefits of a wound-dressing team by reporting our experiences with the establishment of a wound-dressing team. METHODS: The wound-dressing team was established at Korea University Guro Hospital. Between July 2018 and June 2022, 180,872 cases were managed for wounds at the wound-dressing team. The data were analyzed to assess the types of wounds and their outcomes. In addition, questionnaires assessing the satisfaction with the service were administered to patients, ward nurses, residents/internists, and team members. RESULTS: Regarding the wound type, 80,297 (45.3%) were catheter-related, while 48,036 (27.1%), 26,056 (14.7%), and 20,739 (11.7%) were pressure ulcers, dirty wounds, and simple wounds, respectively. In the satisfaction survey, the scores of the patient, ward nurse, dressing team nurse, and physician groups were 8.9, 8.1, 8.2, and 9.1, respectively. Additionally, 136 dressing-related complications (0.08%) were reported. CONCLUSION: The wound dressing team can enhance satisfaction among patients and healthcare providers with low complications. Our findings may provide a potential framework for establishing similar service models.

Incidence and risk factors for pressure injury in hospitalized non-small cell lung cancer patients: A retrospective observational study.

AIM: This study aimed to identify the incidence and risk factors for pressure injury in patients hospitalized for non-small cell lung cancer (NSCLC). METHODS: This retrospective observational study was conducted in 645 adults who were hospitalized for NSCLC. Clinicopathological characteristics were compared between NSCLC patients with pressure injury and those without pressure injury. RESULTS: Among total 645 patients, 180 patients showed pressure injury with an incidence of 27.9%. Patients with pressure injury showed increased serum C-reactive protein (CRP) levels (P < 0.001), increased neutrophil-lymphocyte ratio (P = 0.002), and increased platelet-lymphocyte ratio (P = 0.001) more often. Increase in serum CRP levels at the time of admission was the major risk factor for development of pressure injury in NSCLC patients (OR = 2.20; 95% CI [1.40-3.45]; P = 0.001). Also, among major inflammatory markers, serum CRP levels at the time of admission showed weak negative correlation with the period from admission to the development of pressure injury (r = -0.216, P = 0.004). CONCLUSION: By checking serum CRP levels at the time of admission, the NSCLC patients at high risk for the development of pressure injury can be identified in advance and the occurrence of pressure injury can be reduced by applying more active preventive nursing care. CLINICAL TRIAL REGISTRATION NUMBER: KCT0006570.

Implications of Extended Inhibitory Neuron Development.

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.

Risk Factors for Major Amputation for Midfoot Ulcers in Hospitalized Patients With Diabetes: A Retrospective Study.

PURPOSE: The purpose of this study was to investigate the risk factors for major amputation in persons hospitalized with diabetic foot ulcers involving the midfoot. DESIGN: Retrospective study. SUBJECTS AND SETTING: Between January 2003 and May 2019, a total of 1931 patients with diabetes were admitted to the diabetic wound center for the management of foot ulcers. Among the admitted patients, 169 patients with midfoot ulcers were included in this study. One hundred fifty-four patients (91%) healed without major amputation, while 15 patients (9%) healed post-major amputation. METHODS: Data related to 88 potential risk factors including demographics, ulcer condition, vascularity, bioburden, neurology, and serology were collected from patients in these 2 groups for comparison. Univariate and multivariate logistic regression analyses were performed to analyze risk factors for major amputation. RESULTS: Among the 88 potential risk factors, 15 showed statistically significant differences between the 2 groups. Using univariate analysis of 88 potential risk factors, 8 showed statistically significant differences. Using stepwise multiple logistic regression analysis, 3 of the 8 risk factors remained statistically significant. Multivariate-adjusted odds ratios for deep ulcers invading bone, cardiac disorders, and Charcot foot were 26.718, 18.739, and 16.997, respectively. CONCLUSION: The risk factors for major amputation in patients hospitalized with diabetic midfoot ulcers included deep ulcers invading the bone, cardiac disorders, and Charcot foot.

Demonstration of Solar Cell on a Graphite Sheet with Carbon Diffusion Barrier Evaluation.

An amorphous Si (a-Si) solar cell with a back reflector composed of zinc oxide (ZnO) and silver (Ag) is potentially the most plausible and flexible solar cell if a graphite sheet is used as the substrate. Graphite supplies lightness, conductivity and flexibility to devices. When a graphite sheet is used as the substrate, carbon can diffuse into the Ag layer in the subsequent p-i-n process at 200-400 °C. To prevent this, we added an oxide layer as a carbon diffusion barrier between the carbon substrate and the back reflector. For the carbon diffusion barrier, silicon oxide (SiO2) or tin oxide (SnOx) was used. We evaluated the thermal stability of the back reflector of a carbon substrate using secondary-ion mass spectrometry (SIMS) to analyze the carbon diffusion barrier material. We confirmed the deposition characteristics, reflectance and prevention of carbon diffusion with and without the barrier. Finally, the structures were incorporated into the solar cell and their performances compared. The results showed that the back reflectors that were connected to a carbon diffusion barrier presented better performance, and the reflector with an SnOx layer presented the best performance.

Deep Metabolomics of a High-Grade Serous Ovarian Cancer Triple-Knockout Mouse Model.

High-grade serous carcinoma (HGSC) is the most common and deadliest ovarian cancer (OC) type, accounting for 70-80% of OC deaths. This high mortality is largely due to late diagnosis. Early detection is thus crucial to reduce mortality, yet the tumor pathogenesis of HGSC remains poorly understood, making early detection exceedingly difficult. Faithfully and reliably representing the clinical nature of human HGSC, a recently developed triple-knockout (TKO) mouse model offers a unique opportunity to examine the entire disease spectrum of HGSC. Metabolic alterations were investigated by applying ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to serum samples collected from these mice at premalignant, early, and advanced stages of HGSC. This comprehensive analysis revealed a panel of 29 serum metabolites that distinguished mice with HGSC from controls and mice with uterine tumors with over 95% accuracy. Meanwhile, our panel could further distinguish early-stage HGSC from controls with 100% accuracy and from advanced-stage HGSC with over 90% accuracy. Important identified metabolites included phospholipids, sphingomyelins, sterols, N-acyltaurine, oligopeptides, bilirubin, 2(3)-hydroxysebacic acids, uridine, N-acetylneuraminic acid, and pyrazine derivatives. Overall, our study provides insights into dysregulated metabolism associated with HGSC development and progression, and serves as a useful guide toward early detection.

Analysis of Gastric Microbiota by Pyrosequencing: Minor Role of Bacteria Other Than Helicobacter pylori in the Gastric Carcinogenesis.

BACKGROUND: Little is known about the role of gastric microbiota except for Helicobacter pylori (HP) in human health and disease. We compared the differences of human gastric microbiota according to gastric cancer or control and HP infection status and assessed the role of bacteria other than HP. METHODS: Gastric microbiota of 63 antral mucosal and 18 corpus mucosal samples were analyzed by bar-coded 454 pyrosequencing of the 16S rRNA gene. Antral samples were divided into four subgroups based on HP positivity in pyrosequencing and the presence of cancer. The analysis was focused on bacteria other than HP, especially nitrosating or nitrate-reducing bacteria (NB). The changes of NB in antral mucosa of 16 subjects were followed up. RESULTS: The number of NB other than HP (non-HP-NB) was two times higher in the cancer groups than in the control groups, but it did not reach statistical significance. The number of non-HP-NB tends to increase over time, but this phenomenon was prevented by HP eradication in the HP-positive control group, but not in the HP-positive cancer group. CONCLUSION: We could not find the significant role of bacteria other than HP in the gastric carcinogenesis.

Recurrent DICER1 hotspot mutations in endometrial tumours and their impact on microRNA biogenesis.

DICER1 plays a critical role in microRNA (miRNA) biogenesis. Recurrent somatic 'hotspot' mutations at the four metal-binding sites within the RNase IIIb domain of DICER1 were identified in ovarian sex cord-stromal tumours and have since been described in other paediatric tumours. In this study, we screened the RNase IIIb domain of DICER1 in 290 endometrial tumours and identified six cases with hotspot mutations, including two cases affected by an atypical G1809R mutation directly adjacent to a metal-binding site. Using Illumina and Sanger targeted resequencing, we observed and validated biallelic DICER1 mutations in several cases with hotspot mutations. Through in vitro DICER1 cleavage assays, small RNA deep sequencing and real-time PCR, we demonstrated that mutations adding a positively charged side chain to residue 1809 have similar detrimental effects on 5p miRNA production to mutations at the metal-binding sites. As expected, 5p miRNAs were globally reduced in tumours and cell lines with hotspot mutations. Pathway analysis of gene expression profiles indicated that genes de-repressed due to loss of 5p miRNAs are strongly associated with pathways regulating the cell cycle. Using a Dicer1-null mouse cell line model, we found that expression of DICER1 hotspot mutants promoted cell proliferation, whereas wild-type (WT) DICER1 inhibited cell proliferation. Furthermore, targets of let-7 family miRNAs are enriched among the up-regulated genes, suggesting that loss of let-7 may be impacting downstream pathways. Our results reveal that DICER1 hotspot mutations are implicated in common malignancies and may constitute a unique oncogenic pathway.

Metabolomic serum profiling detects early-stage high-grade serous ovarian cancer in a mouse model.

Ovarian cancer is a deadly disease killing more than any other gynecologic cancer. Nonspecific symptoms, combined with a lack of early detection methods, contribute to late diagnosis and low five-year survival rates. High-grade serous carcinoma (HGSC) is the most common and deadliest subtype that results in 90% of ovarian cancer deaths. To investigate metabolic patterns for early detection of this deadly ovarian cancer, Dicer-Pten double knockout (DKO) mice that phenocopy many of the features of metastatic HGSC observed in women were studied. Using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), serum samples from 14 early-stage tumor (ET) DKO mice and 11 controls were analyzed in depth to screen for metabolic signatures capable of differentiating early-stage HGSC from controls. Iterative multivariate classification selected 18 metabolites that, when considered as a panel, yielded 100% accuracy, sensitivity, and specificity for classification. Altered metabolic pathways reflected in that panel included those of fatty acids, bile acids, glycerophospholipids, peptides, and some dietary phytochemicals. These alterations revealed impacts to cellular energy storage and membrane stability, as well as changes in defenses against oxidative stress, shedding new light on the metabolic alterations associated with early ovarian cancer stages.

An Appropriate Cutoff Value for Determining the Colonization of Helicobacter pylori by the Pyrosequencing Method: Comparison with Conventional Methods.

BACKGROUND: Sequencing of 16S ribosomal RNA (rRNA) gene has improved the characterization of microbial communities. It enabled the detection of low abundance gastric Helicobacter pylori sequences even in subjects that were found to be H. pylori negative with conventional methods. The objective of this study was to obtain a cutoff value for H. pylori colonization in gastric mucosa samples by pyrosequencing method. MATERIALS AND METHODS: Gastric mucosal biopsies were taken from 63 subjects whose H. pylori status was determined by a combination of serology, rapid urease test, culture, and histology. Microbial DNA from mucosal samples was amplified by PCR using universal bacterial primers. 16S rDNA amplicons were pyrosequenced. ROC curve analysis was performed to determine the cutoff value for H. pylori colonization by pyrosequencing. In addition, temporal changes in the stomach microbiota were observed in eight initially H. pylori-positive and eight H. pylori-negative subjects at a single time point 1-8 years later. RESULTS: Of the 63 subjects, the presence of H. pylori sequences was detected in all (28/28) conventionally H. pylori-positive samples and in 60% (21/35) of H. pylori-negative samples. The average percent of H. pylori reads in each sample was 0.67 ± 1.09% in the H. pylori-negative group. Cutoff value for clinically positive H. pylori status was approximately 1.22% based on ROC curve analysis (AUC = 0.957; p < .001). Helicobacter pylori was successfully eradicated in five of seven treated H. pylori-positive subjects (71.4%), and the percentage of H. pylori reads in these five subjects dropped from 1.3-95.18% to 0-0.16% after eradication. CONCLUSION: These results suggest that the cutoff value of H. pylori sequence percentage for H. pylori colonization by pyrosequencing could be set at approximately 1%. It might be helpful to analyze gastric microbiota related to H. pylori sequence status.

High-grade serous ovarian cancer arises from fallopian tube in a mouse model.

Although ovarian cancer is the most lethal gynecologic malignancy in women, little is known about how the cancer initiates and metastasizes. In the last decade, new evidence has challenged the dogma that the ovary is the main source of this cancer. The fallopian tube has been proposed instead as the primary origin of high-grade serous ovarian cancer, the subtype causing 70% of ovarian cancer deaths. By conditionally deleting Dicer, an essential gene for microRNA synthesis, and Pten, a key negative regulator of the PI3K pathway, we show that high-grade serous carcinomas arise from the fallopian tube in mice. In these Dicer-Pten double-knockout mice, primary fallopian tube tumors spread to engulf the ovary and then aggressively metastasize throughout the abdominal cavity, causing ascites and killing 100% of the mice by 13 mo. Besides the clinical resemblance to human serous cancers, these fallopian tube cancers highly express genes that are known to be up-regulated in human serous ovarian cancers, also demonstrating molecular similarities. Although ovariectomized mice continue to develop high-grade serous cancers, removal of the fallopian tube at an early age prevents cancer formation--confirming the fallopian tube origin of the cancer. Intriguingly, the primary carcinomas are first observed in the stroma of the fallopian tube, suggesting that these epithelial cancers have a mesenchymal origin. Thus, this mouse model demonstrates a paradigm for the origin and initiation of high-grade serous ovarian carcinomas, the most common and deadliest ovarian cancer.