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BACKGROUND: Schwannomas in the renal hilum are rare among retroperitoneal tumors. However, the possibility of malignant findings cannot be ruled out, and surgery is often indicated. This case was expected to be difficult to remove laparoscopically because the tumor was sandwiched between the arteriovenous veins of the renal portal. Sometimes, the tumor should be resected with a conservative approach to the kidney to preserve the renal function. CASE PRESENTATION: Our patient was a 51-year-old Asian-Japanese man who was referred to our department for a retroperitoneal tumor in the renal hilum. Since malignancy could not be ruled out due to its size (45 × 48 × 55 mm) on imaging, the tumor was excised laparoscopically. Histopathology revealed schwannoma. CONCLUSIONS: We herein report a case in which a renal hilar tumor between renal arteriovenous vessels was successfully resected laparoscopically.
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Laparoscopía , Neurilemoma , Neoplasias Retroperitoneales , Humanos , Neurilemoma/cirugía , Neurilemoma/diagnóstico por imagen , Neurilemoma/patología , Masculino , Persona de Mediana Edad , Neoplasias Retroperitoneales/cirugía , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/patología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Riñón/irrigación sanguínea , Riñón/cirugía , Riñón/patologíaRESUMEN
BACKGROUND: Ewing's sarcoma is a primary bone tumor predominantly observed in children and adolescents, necessitating a multidisciplinary treatment approach. While localized cases have a 5-year survival rate of 60-70%, the prognosis is significantly worse in pelvic advanced cases with metastasis. Moreover, pelvic Ewing's sarcoma has the unique problem of leading to high rates of postoperative infection. CASE PRESENTATION: We present the case of a Japanese 14-year-old boy with left iliac Ewing's sarcoma and multiple metastases. At the initial visit, imaging revealed a large tumor in the left iliac bone with extraosseous extension and metastasis to multiple sites. Neoadjuvant chemotherapy resulted in significant tumor reduction. Surgical resection was performed without pelvic ring reconstruction to enable early postoperative chemotherapy and minimize postoperative infection risk. Despite complete abductor muscle removal, the patient achieved a stable gait postoperatively by centering the load axis. CONCLUSION: Our case highlights the successful management of a left iliac Ewing's sarcoma with multiple metastases, with a focus on functional preservation and infection risk reduction. Pelvic ring reconstruction was not performed to avoid postoperative complications, emphasizing the importance of early postoperative chemotherapy. The patient achieved a stable gait postoperatively, demonstrating the potential benefits of this approach in similar cases.
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Neoplasias Óseas , Ilion , Sarcoma de Ewing , Caminata , Humanos , Sarcoma de Ewing/cirugía , Masculino , Neoplasias Óseas/cirugía , Neoplasias Óseas/secundario , Adolescente , Ilion/trasplante , Huesos Pélvicos/cirugía , Huesos Pélvicos/diagnóstico por imagen , Procedimientos de Cirugía Plástica/métodos , Resultado del Tratamiento , Terapia NeoadyuvanteRESUMEN
This study aimed to assess the applicability of solution-state 1H NMR for molecular-level characterization of siRNA-loaded lipid nanoparticles (LNP). Dilinoleylmethyl-4-dimethylaminobutyrate (DLin-MC3-DMA, MC3) was used as an ionizable lipid, and siRNA-loaded LNPs were prepared by pre-mixing and post-mixing methods. The pre-mixing method involved mixing an acidic solution containing siRNA with an ethanolic lipid solution using a microfluidic mixer. The pre-mixed LNP was prepared by dialyzing the mixed solution into the phosphate buffered saline (PBS, pH 7.4). The post-mixed LNP was prepared by mixing the siRNA solution with empty LNP in an acidic condition with and without ethanol, resulting in post-mixed LNP (A) and (B), respectively. Both pre-mixed and post-mixed LNPs formed LNP particles with an average diameter of approximately 50 nm. Moreover, the ratio of encapsulated siRNA to lipid content in each LNP particle remained constant regardless of the preparation method. However, small-angle X-ray scattering measurements indicated structural variations in the siRNA-MC3 stacked bilayer structure formed in the LNPs, depending on the preparation method. Solution-state 1H NMR analysis suggested that the siRNA was incorporated uniformly into the LNP core for pre-mixed LNP compared to post-mixed LNPs. In contrast, the post-mixed LNPs contained siRNA-empty regions with local enrichment of siRNA in the LNP core. This heterogeneity was more pronounced in post-mixed LNP (B) than in post-mixed LNP (A), suggesting that ethanol facilitated the homogeneous mixing of siRNA with LNP lipids. The silencing effect of each siRNA-loaded LNP was reduced in the order of pre-mixed LNP, post-mixed LNP (A), and post-mixed LNP (B). This suggested that the heterogeneity of the siRNA-loaded LNP could cause a reduction in the silencing effect of the incorporated siRNA inside LNPs. The present study highlighted that NMR-based characterization of siRNA-loaded LNP can reveal the molecular-level heterogeneity of siRNA-loaded LNP, which helps to optimize the preparation conditions of siRNA-loaded LNP formulations.
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Background: Traumatic pneumocephalus is commonly encountered after basal skull fractures and rarely associated with blunt chest trauma. Here, we report a case of pneumocephalus caused by traumatic pneumothorax and brachial plexus avulsion. Case Presentation: A 20-year-old male was admitted to our hospital following a motorcycle accident with complete paralysis of the right upper limb. 2 days later, follow-up computed tomography revealed a slight right pneumothorax, pneumomediastinum around the neck, and intracranial air without skull fracture. Air migrates into the subarachnoid space through a dural tear caused by a brachial plexus avulsion. The pneumocephalus immediately improved after the insertion of a chest drain. Conclusion: Pneumothorax combined with brachial plexus avulsion could lead to pneumocephalus. Immediate chest drainage might be the best way to stop the migration of air; however, care should be taken to not worsen cerebrospinal fluid leakage.
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Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (-â 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup.
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Introduction: Sperm immobility is a condition in which sperm are viable but not motile. We reported three patients with sperm immobility, who underwent testicular sperm extraction-intracytoplasmic sperm injection. Case presentation: In case 1, a 32-year-old patient with sperm immobility had previously undergone intracytoplasmic sperm injection with ejaculated sperm; however, pregnancy was unsuccessful. testicular sperm extraction-intracytoplasmic sperm injection was performed at our clinic, and pregnancy was achieved. In case 2, a 23-year-old patient with clinical varicocele whose semen analysis revealed sperm immobility underwent varicocelectomy, without improvement. Using the hypo-osmotic swelling test technique, testicular sperm extraction-intracytoplasmic sperm injection was performed; however, pregnancy was not achieved. In case 3, a 44-year-old patient with sperm immobility underwent testicular sperm extraction, and motile sperm were retrieved. testicular sperm extraction-intracytoplasmic sperm injection using these sperm resulted in pregnancy. Conclusion: Although testicular sperm extraction-intracytoplasmic sperm injection is not considered a solution in patients with sperm immobility, pregnancies were achieved. testicular sperm extraction-intracytoplasmic sperm injection may be successful in some cases in which ejaculated sperm intracytoplasmic sperm injection is unsuitable.
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Approximately 1% of the general male population has azoospermia, and nonobstructive azoospermia accounts for the majority of cases. The causes vary widely, including chromosomal and genetic abnormalities, varicocele, drug-induced causes, and gonadotropin deficiency; however, the cause is often unknown. In azoospermia caused by hypogonadotropic hypogonadism, gonadotropin replacement therapy can be expected to produce sperm in the ejaculate. In some cases, upfront varicocelectomy for nonobstructive azoospermia with varicocele may result in the appearance of ejaculated spermatozoa; however, the appropriate indication should be selected. Each guideline recommends microdissection testicular sperm extraction for nonobstructive azoospermia in terms of successful sperm retrieval and avoidance of complications. Sperm retrieval rates generally ranged from 20% to 70% but vary depending on the causative disease. Various attempts have been made to predict sperm retrieval and improve sperm retrieval rates; however, the evidence is insufficient. Further evidence accumulation is needed for salvage treatment in cases of failed sperm retrieval. In Japan, there is inadequate provision on the right to know the origin of children born from artificial insemination of donated sperm and the rights of sperm donors, as well as information on unrelated family members, and the development of these systems is challenging. In the future, it is hoped that the pathogenesis of nonobstructive azoospermia with an unknown cause will be elucidated and that technology for omics technologies, human spermatogenesis using pluripotent cells, and organ culture methods will be developed.
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Azoospermia , Varicocele , Niño , Humanos , Masculino , Azoospermia/etiología , Azoospermia/terapia , Varicocele/complicaciones , Varicocele/cirugía , Microdisección/efectos adversos , Semen , Estudios Retrospectivos , Gonadotropinas , Testículo/patologíaRESUMEN
Introduction: Malignant bone and soft tissue tumors, commonly called sarcomas, predominantly originate in bone and soft tissues and typically affect individuals at a younger age. Following the resection of the primary tumor, treatment often necessitates radiation therapy and gonadotoxic chemotherapy, the specifics of which depend on the disease's stage Conversely, there is a notable concern regarding the potential loss of fertility due to these treatments. Consequently, it is recommended that men consider sperm cryopreservation before initiating treatment. This study aims to assess spermatogenesis in male patients diagnosed with malignant bone and soft tissue tumors before and after chemotherapy. Methods: This study involved 34 male patients diagnosed with malignant bone and soft tissue tumors and subsequently underwent sperm cryopreservation before initiating treatment. Medical records included details about the primary disease, age, marital status at presentation, semen analysis results, treatment regimen and number of courses, post-treatment semen analysis, renewal status and outcomes. Results: The mean age at the time of sperm cryopreservation was 22.8 years. The median semen volume was 2.5 mL, sperm concentration was 32.6 million/ml, and sperm motility was 38.5%. Following chemotherapy, semen analysis was conducted on 12 patients, with ifosfamide being the predominant drug used in all cases. Among these 12 patients, eight retained viable spermatozoa, and two successfully achieved spontaneous pregnancies resulting in live births. In one of the remaining four cases where no sperm were detected in ejaculate, a live birth was achieved through intracytoplasmic sperm injection using cryopreserved sperm. Discussion: While ifosfamide, the primary chemotherapy drug for patients with malignant bone and soft tissue tumors, was associated with severe impairments in spermatogenesis, recovery of spermatogenesis was observed in many cases. However, there were instances of prolonged azoospermia. Even in such cases, assisted reproduction using cryopreserved sperm remained viable for achieving parenthood. In light of these findings, offering patients the opportunity for fertility preservation is advisable.
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BACKGROUND: Late-onset hypogonadism (LOH) is a condition caused by the decline of testosterone levels with aging and is associated with various symptoms, including lower urinary tract symptoms (LUTSs). Although some reports have shown that testosterone replacement treatment for LOH improves LUTSs, no large study has revealed a correlation between LUTSs and LOH. This study investigated the correlation between the severity of LOH and LUTSs in Japanese males >40 years of age using a web-based questionnaire with the Aging Males' Symptoms (AMS) scale. METHODS: We asked 2000 Japanese males to answer both the AMS and IPSS/QOL questionnaires using a web-based survey. Among these 2000 individuals, 500 individuals were assigned to each age group. RESULTS: The IPSS total score was positively correlated with the severity of AMS (shown as median [mean ± SD]): no/little group, 2 (3.67 ± 5.36); mild group, 6 (7.98 ± 6.91); moderate group, 11 (12.49 ± 8.63); and severe group, 16 (14.83 ± 9.24) (p < 0.0001). CONCLUSIONS: Individuals with higher AMS values, representing cases with severe LOH symptoms, had a higher risk of experiencing nocturia and LUTSs than those with lower AMS values.
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BACKGROUND: The Mitrofanoff (appendicovesicostomy) procedure is a contraindicated urinary modification that maintains urinary continence by forming a flap-valve mechanism at the site of anastomosis between the appendage and bladder wall, which is used as a guide for urinary drainage. This technique has been used by intermittent self-catheterization patients who have difficulty voiding from the native urethra or in cases where voiding from the abdominal wall would improve quality of life. However, the risk of stone formation is high due to intermittent urinary catheterization using the Mitrofanoff conduit urethrostomy as a conduit. CASE PRESENTATION: The patient was a 22-year-old Asian-Japanese woman. At 6 years of age, she underwent bilateral vesicoureteral reflux surgery, Mitrofanoff urethrostomy using the appendix, abdominal wall plication, and vaginoplasty using the ileum. During follow-up, ultrasound performed due to persistent pain during urinary drainage revealed a 26 mm bladder stone. We performed ureteroscopic lithotripsy 6Fr using ureteral access sheath and made lithotripsy using Ho: YAG laser, then successfully removed the target stone. CONCLUSIONS: We report a case of transurethral laser lithotripsy using the Mitrofanoff urethral conduit for bladder stones. Using with ureteral access sheath made lithotripsy and retrieved ureteral stone more effective.
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Litotripsia por Láser , Litotricia , Cálculos de la Vejiga Urinaria , Femenino , Humanos , Adulto Joven , Adulto , Litotripsia por Láser/métodos , Cálculos de la Vejiga Urinaria/cirugía , Uretra/cirugía , Calidad de Vida , Litotricia/métodosRESUMEN
BACKGROUND: Greater trochanter (GT) fractures are rare and frequently associated with occult intertrochanteric (IT) fractures. No consensus has been reached regarding whether surgical or conservative treatment is preferred for such fractures. The purpose of this study was to evaluate the clinical outcomes of surgical versus conservative treatment for coexistent GT and occult IT fractures. MATERIALS AND METHODS: Between January 2006 and December 2021, we enrolled patients who were diagnosed with GT fracture on radiography or CT and underwent MRI to reveal occult IT fracture. Eligible patients were divided into two treatment groups: surgical and conservative treatment. The characteristics and outcomes of the patients were compared between the two groups. RESULTS: Fifty patients were included in this study. There were 29 patients (3 male, 26 female; mean age: 84.45 ± 10.68 years) in the surgical treatment group and 21 patients (3 male, 18 female; mean age: 83.33 ± 9.34 years) in the conservative group, respectively. The demographic and clinical characteristics of the two groups were comparable, including sex, age, body mass index (BMI), percentage of extension into the IT area, days from injury to diagnosis, and activities of daily living (ADL) before injury. All 50 patients healed without displaced fractures, regardless of the percentage of extension into the IT area. There were no significant differences in the modified functional ambulation category scores between the two groups at one week, one month, and three months following the start of the treatment intervention (P = 0.653, 0.923, and 0.577, respectively). The length of hospital stay was 48.4 ± 5.97 days in the surgical treatment group and 50.6 ± 7.55 days in the conservative treatment group (P = 0.422). There was no significant difference in one-year mortality between surgical and conservative treatments (P = 0.219). CONCLUSIONS: There were no significant differences in any outcome between the surgical and nonsurgical treatment groups. The results of the study suggested that coexistent GT and occult IT fractures may be managed conservatively without developing complete fractures, regardless of extension into the IT area.
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Fracturas Cerradas , Fracturas de Cadera , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Tratamiento Conservador , Estudios Retrospectivos , Actividades Cotidianas , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Radiografía , Resultado del Tratamiento , Fracturas Cerradas/cirugíaRESUMEN
Despite advanced therapeutics, esophageal squamous cell carcinoma (ESCC) remains one of the deadliest cancers. Here, we propose a novel therapeutic strategy based on synthetic lethality combining trifluridine/tipiracil and MK1775 (WEE1 inhibitor) as a treatment for ESCC. This study demonstrates that trifluridine induces single-strand DNA damage in ESCC cells, as evidenced by phosphorylated replication protein 32. The DNA damage response includes cyclin-dependent kinase 1 (CDK1) (Tyr15) phosphorylation as CDK1 inhibition and a decrease of the proportion of phospho-histone H3 (p-hH3)-positive cells, indicating cell cycle arrest at the G2 phase before mitosis entry. The WEE1 inhibitor remarkedly suppressed CDK1 phosphorylation (Try15) and reactivated CDK1, and also increased the proportion of p-hH3-positive cells, which indicates an increase of the number of cells into mitosis. Trifluridine combined with a WEE1 inhibitor increased trifluridine-mediated DNA damage, namely DNA double-strand breaks, as shown by increased γ-H2AX expression. Moreover, the combination treatment with trifluridine/tipiracil and a WEE1 inhibitor significantly suppressed tumor growth of ESCC-derived xenograft models. Hence, our novel combination treatment with trifluridine/tipiracil and a WEE1 inhibitor is considered a candidate treatment strategy for ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Trifluridina/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Fosforilación , Histonas , Proteínas de Ciclo Celular , Línea Celular Tumoral , Proteínas Tirosina QuinasasRESUMEN
1H NMR relaxometry was applied for molecular-level structural analysis of siRNA-loaded lipid nanoparticles (LNPs) to clarify the impact of the neutral lipids, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol, on the physicochemical properties of LNP. Incorporating DSPC and cholesterol in ionizable lipid-based LNP decreased the molecular mobility of ionizable lipids. DSPC reduced the overall molecular mobility of ionizable lipids, while cholesterol specifically decreased the mobility of the hydrophobic tails of ionizable lipids, suggesting that cholesterol filled the gap between the hydrophobic tails of ionizable lipids. The decrease in molecular mobility and change in orientation of lipid mixtures contributed to the maintenance of the stacked bilayer structure of siRNA and ionizable lipids, thereby increasing the siRNA encapsulation efficiency. Furthermore, NMR relaxometry revealed that incorporating those neutral lipids enhanced PEG chain flexibility at the LNP interface. Notably, a small amount of DSPC effectively increased PEG chain flexibility, possibly contributing to the improved dispersion stability and narrower size distribution of LNPs. However, cryogenic transmission electron microscopy represented that adding excess amounts of DSPC and cholesterol into LNP resulted in the formation of deformed particles and demixing cholesterol within the LNP, respectively. The optimal lipid composition of ionizable lipid-based LNPs in terms of siRNA encapsulation efficiency and PEG chain flexibility was rationalized based on the molecular-level characterization of LNPs. Moreover, the NMR relaxation rate of tertiary amine protons of ionizable lipids, which are the interaction site with siRNA, can be a valuable indicator of the encapsulated amount of siRNA within LNPs. Thus, NMR-based analysis can be a powerful tool for efficiently designing LNP formulations and their quality control based on the molecular-level elucidation of the physicochemical properties of LNPs.
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Imagen por Resonancia Magnética , Protones , ARN Interferente Pequeño , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
With advances in cancer treatment, such as cytotoxic chemotherapy and radiotherapy, grave new sequelae of treatment have emerged for young cancer survivors. One sequela that cannot be overlooked is male infertility, with reportedly 15% to 30% of cancer survivors losing their fertility potential. Cytotoxic therapy influences spermatogenesis at least temporarily, and in some cases, permanently. The degree of spermatogenesis impairment depends on the combination of drugs used, their cumulative dose, and the level of radiation. The American Society of Clinical Oncology has created an index to classify the risks to fertility based on treatment. Medical professionals currently use this risk classification in fertility preservation (FP) programs. FP programs are currently being promoted to prevent spermatogenesis failure resulting from cancer treatment. For patients who are able to ejaculate and whose semen contains sperm, the semen (sperm) is cryopreserved. Moreover, for patients who lack the ability to ejaculate, those with azoospermia or severe oligozoospermia, and those who have not attained puberty (i.e., spermatogenesis has not begun), testicular biopsy is performed to collect the sperm or germ cells and cryopreserve them. This method of culturing germ cells to differentiate the sperm has been successful in some animal models, but not in humans. FP has recently gained popularity; however, some oncologists and medical professionals involved in cancer treatment still lack adequate knowledge of these procedures. This hinders the dissemination of information to patients and the execution of FP. Information sharing and collaboration between reproductive medicine specialists and oncologists is extremely important for the development of FP. In Japan, the network of clinics and hospitals that support FP is expanding across prefectures.
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Background: Atlantoaxial rotatory fixation (AARF) is extremely rare in adults, and there is no consensus on the ideal treatment of adult AARF because of its rarity. We presented a case series of three adult AARFs and reviewed the literature on adult AARFs. We suggest treatment guidelines for the injury based on the literature review. Methods: We compiled a series of three adult AARFs seen in our hospital. We also utilized the NCBI library to retrieve literature on adult AARF from 2000 to 2021. We included articles on adult AARF, which described the number of days from injury to diagnosis, Fielding classification, occurrence of associated cervical injuries, and details of treatment and the results. Results: Thirty adult AARFs reports fulfilled the criteria and 32 patients were analyzed. Eighteen patients had Fielding Type 1 AARF and were diagnosed within 1 month of injury. Among them, 13 cases healed with conservative treatment. Patients with acute AARF of Fielding Type 1 who underwent manual reduction healed successfully. All patients that required more than 1 month from injury to diagnosis underwent surgery. All cases with AARF Fielding Types 2, 3, and 4 failed conservative treatment. Conclusion: The case series and literature review suggest that early diagnosis of adult AARF is essential for successful closed reduction, and the Fielding classification may help determine treatment strategy. Furthermore, this study showed that not only traction but also manual reduction may be a useful treatment for early diagnosed AARF Fielding Type 1 without complications. Level of Evidence: III.
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Articulación Atlantoaxoidea , Luxaciones Articulares , Adulto , Humanos , Articulación Atlantoaxoidea/diagnóstico por imagen , Articulación Atlantoaxoidea/cirugía , Articulación Atlantoaxoidea/lesiones , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/cirugíaRESUMEN
Background: Newly emerging serious post-treatment complications among young male cancer survivors involve fertility and sexual function, preventing them from pursuing a normal family life. Methods: We studied and summarized published studies that assess the relationship between cancer treatments and reduced spermatogenesis or sexual dysfunction. Main findings: Infertility often occurs because of anticancer therapies that impair spermatogenesis. While some patients postremission functionally recover fertility, others experience a decreased sperm count and azoospermia. Fertility-preserving modalities are currently being promoted worldwide to preserve spermatogenesis following cancer therapy. Patients who can ejaculate and have sperm in their semen should cryopreserve semen. However, for patients who have never ejaculated before puberty or in whom spermatogenesis has not been established, testis biopsy is performed to collect and preserve sperm or germ cells. Fertility preservation is gaining popularity and requires continuous information dissemination to oncologists and cancer treatment professionals. Furthermore, male sexual dysfunction predominantly involves erectile dysfunction and ejaculation disorder. Conclusion: Although preventive and therapeutic methods for these disorders have been established within urology, patients and medical professionals in other fields remain uninformed of these advances. Therefore, dissemination of information regarding fertility preservation techniques should be accelerated.
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Clinical cancer genome sequencing detects oncogenic variants that are potential targets for cancer treatment, but it also detects variants of unknown significance. These variants may interact with each other to influence tumor pathophysiology, however, such interactions have not been fully elucidated. Additionally, the effect of target therapy for those variants also unclarified. In this study, we investigated the biological functions of a HER2 mutation (G776S mutation) of unknown pathological significance, which was detected together with APC mutation by cancer genome sequencing of samples from a colorectal cancer (CRC) patient. Transfection of the HER2 G776S mutation alone slightly increased the kinase activity and phosphorylation of HER2 protein, but did not activate HER2 downstream signaling or alter the cell phenotype. On the other hand, the HER2 G776S mutation was shown to have strong oncogenic potential when loss of APC function was accompanied. We revealed that loss of APC function increased Wnt pathway activity but also increased RAS-GTP, which increased ERK phosphorylation triggered by HER2 G776S transfection. In addition, afatinib, a pan-HER tyrosine kinase inhibitor, suppressed tumor growth in xenografts derived from HER2 G776S-transfected CRC cells. These findings suggest that this HER2 mutation in CRC may be a potential therapeutic target.
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Neoplasias Colorrectales , Oncogenes , Carcinogénesis/genética , Neoplasias Colorrectales/genética , Humanos , Mutación , Fosforilación , Agitación PsicomotoraRESUMEN
The prevention and treatment of mental illness is a serious social issue. Prediction and intervention, however, have been difficult because of lack of objective biomarkers for mental illness. The objective of this study was to use biometric data acquired from wearable devices as well as medical examination data to build a predictive model that can contribute to the prevention of the onset of mental illness. This was an observational study of 4,612 subjects from the health database of society-managed health insurance in Japan provided by JMDC Inc. The inputs to the predictive model were 3-months of continuous wearable data and medical examinations within and near that period; the output was the presence or absence of mental illness over the following month, as defined by insurance claims data. The features relating to the wearable data were sleep, activity, and resting heart rate, measured by a consumer-grade wearable device (specifically, Fitbit). The predictive model was built using the XGBoost algorithm and presented an area-under-the-receiver-operating-characteristic curve of 0.712 (SD = 0.02, a repeated stratified group 10-fold cross validation). The top-ranking feature importance measure was wearable data, and its importance was higher than the blood-test values from medical examinations. Detailed verification of the model showed that predictions were made based on disrupted sleep rhythms, mild physical activity duration, alcohol use, and medical examination data on disrupted eating habits as risk factors. In summary, the predictive model showed useful accuracy for grouping the risk of mental illness onset, suggesting the potential of predictive detection, and preventive intervention using wearable devices. Sleep abnormalities in particular were detected as wearable data 3 months prior to mental illness onset, and the possibility of early intervention targeting the stabilization of sleep as an effective measure for mental illness onset was shown.