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1.
J Clin Med ; 13(9)2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38731247

RESUMEN

Background: The application of personalized cancer treatment based on genetic information and surgical samples has begun in the field of cancer medicine. However, a biopsy may be painful for patients with advanced diseases that do not qualify for surgical resection. Patient-derived xenografts (PDXs) are cancer models in which patient samples are transplanted into immunodeficient mice. PDXs are expected to be useful for personalized medicine. The aim of this study was to establish a PDX from body fluid (PDX-BF), such as peritoneal and pleural effusion samples, to provide personalized medicine without surgery. Methods: PDXs-BF were created from patients with ovarian cancer who had positive cytology findings based on peritoneal and pleural effusion samples. PDXs were also prepared from each primary tumor. The pathological findings based on immunohistochemistry were compared between the primary tumor, PDX, and PDX-BF. Further, genomic profiles and gene expression were evaluated using DNA and RNA sequencing to compare primary tumors, PDXs, and PDX-BF. Results: Among the 15 patients, PDX-BF was established for 8 patients (5 high-grade serous carcinoma, 1 carcinosarcoma, 1 low-grade serous carcinoma, and 1 clear cell carcinoma); the success rate was 53%. Histologically, PDXs-BF have features similar to those of primary tumors and PDXs. In particular, PDXs-BF had similar gene mutations and expression patterns to primary tumors and PDXs. Conclusions: PDX-BF reproduced primary tumors in terms of pathological features and genomic profiles, including gene mutation and expression. Thus, PDX-BF may be a potential alternative to surgical resection for patients with advanced disease.

2.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338763

RESUMEN

Patient-derived xenograft (PDX) models retain the characteristics of tumors and are useful tools for personalized therapy and translational research. In this study, we aimed to establish PDX models for uterine corpus malignancies (UC-PDX) and analyze their similarities. Tissue fragments obtained from 92 patients with uterine corpus malignancies were transplanted subcutaneously into immunodeficient mice. Histological and immunohistochemical analyses were performed to compare tumors of patients with PDX tumors. DNA and RNA sequencing were performed to validate the genetic profile. Furthermore, the RNA in extracellular vesicles (EVs) extracted from primary and PDX tumors was analyzed. Among the 92 cases, 52 UC-PDX models were established, with a success rate of 56.5%. The success rate depended on tumor histology and staging. The pathological and immunohistochemical features of primary and PDX tumors were similar. DNA sequencing revealed similarities in gene mutations between the primary and PDX tumors. RNA sequencing showed similarities in gene expressions between primary and PDX tumors. Furthermore, the RNA profiles of the EVs obtained from primary and PDX tumors were similar. As UC-PDX retained the pathological and immunohistochemical features and gene profiles of primary tumors, they may provide a platform for developing personalized medicine and translational research.


Asunto(s)
Neoplasias Uterinas , Femenino , Humanos , Animales , Ratones , Xenoinjertos , Modelos Animales de Enfermedad , Neoplasias Uterinas/genética , Mutación , ARN , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Mol Cancer ; 22(1): 185, 2023 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-37980528

RESUMEN

BACKGROUND: Currently, only limited knowledge is available regarding the phenotypic association between fibroblast growth factor receptor 3 (FGFR3) alterations and the tumor microenvironment (TME) in bladder cancer (BLCA). METHODS: A multi-omics analysis on 389 BLCA and 35 adjacent normal tissues from a cohort of OMPU-NCC Consortium Japan was retrospectively performed by integrating the whole-exome and RNA-sequence dataset and clinicopathological record. A median follow-up duration of all BLCA cohort was 31 months. RESULTS: FGFR3 alterations (aFGFR3), including recurrent mutations and fusions, accounted for 44% of non-muscle invasive bladder cancer (NMIBC) and 15% of muscle-invasive bladder cancer (MIBC). Within MIBC, the consensus subtypes LumP was significantly more prevalent in aFGFR3, whereas the Ba/Sq subtype exhibited similarity between intact FGFR3 (iFGFR3) and aFGFR3 cases. We revealed that basal markers were significantly increased in MIBC/aFGFR3 compared to MIBC/iFGFR3. Transcriptome analysis highlighted TIM3 as the most upregulated immune-related gene in iFGFR3, with differential immune cell compositions observed between iFGFR3 and aFGFR3. Using EcoTyper, TME heterogeneity was discerned even within aFGFR cases, suggesting potential variations in the response to checkpoint inhibitors (CPIs). Among 72 patients treated with CPIs, the objective response rate (ORR) was comparable between iFGFR3 and aFGFR3 (20% vs 31%; p = 0.467). Strikingly, a significantly higher ORR was noted in LumP/aFGFR3 compared to LumP/iFGFR3 (50% vs 5%; p = 0.022). This trend was validated using data from the IMvigor210 trial. Additionally, several immune-related genes, including IDO1, CCL24, IL1RL1, LGALS4, and NCAM (CD56) were upregulated in LumP/iFGFR3 compared to LumP/aFGFR3 cases. CONCLUSIONS: Differential pathways influenced by aFGFR3 were observed between NMIBC and MIBC, highlighting the upregulation of both luminal and basal markers in MIBC/aFGFR3. Heterogeneous TME was identified within MIBC/aFGFR3, leading to differential outcomes for CPIs. Specifically, a favorable ORR in LumP/aFGFR3 and a poor ORR in LumP/iFGFR3 were observed. We propose TIM3 as a potential target for iFGFR3 (ORR: 20%) and several immune checkpoint genes, including IDO1 and CCL24, for LumP/iFGFR3 (ORR: 5%), indicating promising avenues for precision immunotherapy for BLCA.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias de la Vejiga Urinaria , Humanos , Pronóstico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Biomarcadores de Tumor/genética , Estudios Retrospectivos , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Microambiente Tumoral , Receptor 2 Celular del Virus de la Hepatitis A , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología
4.
Cancer Sci ; 114(12): 4622-4631, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37752769

RESUMEN

Emerging evidence suggests that the presence of tertiary lymphoid structures (TLS) and neutrophil-lymphocyte ratio (NLR) in peripheral blood is associated with the treatment response to checkpoint inhibitors (CPIs), whereas there is limited knowledge regarding whether these factors reciprocally impact the treatment outcomes of CPIs in metastatic urothelial carcinoma (mUC). Herein, we investigated treatment outcomes of platinum-refractory mUC patients (50 cases with whole-exome and transcriptome sequencing) treated with pembrolizumab. The pathological review identified 24% of cases of TLS in the specimens. There was no significant difference in the NLR between the TLS- and TLS+ groups (p = 0.153). In the lower NLR group, both overall survival and progression-free survival were significantly longer in patients with TLS than in those without TLS, whereas the favorable outcomes associated with TLS were not observed in patients in the higher NLR group. We explored transcriptomic differences in UC with TLS. The TLS was comparably observed between luminal (20%) and basal (25%) tumor subtypes (p = 0.736). Exploring putative immune-checkpoint genes revealed that ICOSLG (B7-H2) was significantly increased in tumors with lower NLR. KRT expression levels exhibited higher basal cell markers (KRT5 and KRT17) in the higher NLR group and lower differentiated cell markers (KRT8 and KRT18) in patients with TLS. In conclusion, the improved outcomes of pembrolizumab treatment in mUC are restricted to patients with lower NLR. Our findings begin to elucidate a distinct molecular pattern for the presence of TLS according to the NLR in peripheral blood.


Asunto(s)
Carcinoma de Células Transicionales , Estructuras Linfoides Terciarias , Neoplasias de la Vejiga Urinaria , Humanos , Neutrófilos , Linfocitos , Pronóstico , Estudios Retrospectivos
5.
J Clin Med ; 12(13)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37445574

RESUMEN

Sentinel node biopsy (SNB) is performed worldwide in patients with endometrial cancer (EC). The aim of this study was to evaluate and compare the occurrence rate of lymphatic complications between SNB and pelvic lymphadenectomy (LND) for EC. The medical records of women who underwent SNB or pelvic LND for EC between September 2012 and April 2022 were assessed. A total of 388 patients were enrolled in the current study. Among them, 201 patients underwent SNB and 187 patients underwent pelvic LND. The occurrence rates of lower-extremity lymphedema (LEL) and pelvic lymphocele (PL) were compared between the patients who underwent SNB and those who underwent pelvic LND. The SNB group had a significantly lower occurrence rate of lower-extremity LEL than the pelvic LND group (2.0% vs. 21.3%, p < 0.01). There were no patients who had PL in the SNB group; however, 4 (2.1%) patients in the pelvic LND group had PL. The occurrence rates of lower-extremity LEL and PL were significantly lower in patients who underwent SNB than those who underwent pelvic LND. SNB for EC has a lower risk of lymphatic complications compared to systemic LND.

6.
Ultramicroscopy ; 250: 113754, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37186985

RESUMEN

Previous studies have shown that type-II magnetic-domain contrasts are caused by differences in the backscattering yields of magnetic domains of opposite magnetisation. Imaging the magnetic domains when the magnetisation vectors in the opposite-magnetisation domains are perpendicular to the tilt axis of the specimen has been considered difficult, because of the lack of change in the backscattering yields between the domains. An alternative way to obtain the type-II magnetic-domain contrasts is to utilise the difference in the exit angular distribution of the backscattered electrons from different magnetic domains. In this study, it is found that an electron backscatter diffraction (EBSD) camera can be used to obtain the type-II magnetic-domain contrasts caused by the above two mechanisms simultaneously. We verify this by distinguishing all four possible in-plane magnetisation vectors on a Fe-Si (001) surface without a sample rotation, using an EBSD detector as an array of electron detectors. The change in contrast between the magnetic domains, with respect to the location of a virtual electron detector, can provide information on the directions of the magnetisation vectors. A method to suppress the topographic contrast superimposed on the magnetic-domain contrast is also demonstrated.

7.
Appl Radiat Isot ; 197: 110792, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37062147

RESUMEN

There are few studies about boron neutron capture therapy (BNCT) for cervical cancer. The present study evaluated the biodistribution of boronophenylalanine (BPA) and the effect of BNCT on cervical cancer cell lines. BPA exposure and neutron irradiation of cervical cancer cell lines resulted in decreased survival fraction compared to irradiation only. In vivo cervical cancer tumor boron concentration was highest at 2.5 h after BPA intraperitoneal administration, and higher than in the other organs. BNCT may be effective against cervical carcinoma.


Asunto(s)
Terapia por Captura de Neutrón de Boro , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Boro/uso terapéutico , Terapia por Captura de Neutrón de Boro/métodos , Distribución Tisular , Compuestos de Boro/uso terapéutico
8.
Gynecol Oncol ; 170: 70-76, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36638744

RESUMEN

OBJECTIVE: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. METHODS: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-µm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. RESULTS: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. CONCLUSIONS: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.


Asunto(s)
Neoplasias de la Mama , Neoplasias Endometriales , Ácidos Nucleicos , Humanos , Femenino , Metástasis Linfática/patología , Estudios Prospectivos , Técnicas de Amplificación de Ácido Nucleico/métodos , Neoplasias Endometriales/patología , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela , Queratina-19/genética , Neoplasias de la Mama/patología
9.
FEBS J ; 290(8): 2085-2096, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36416563

RESUMEN

Analysis of ovarian cancer tissue and normal ovarian tissue revealed 31 RNA modifications with significant differences observed in cancer tissue compared with normal tissue. Moreover, we found Im and chm5U as characteristic RNA modifications in advanced and platinum-resistant ovarian cancers, respectively. Considering that these differences in RNA modifications may be due to the intra-tumour microenvironment, we xenografted the ovarian cancer cell line RMG-1 to create RMG-1 tumours and compared them with original RMG-1 cells. As a result, 14 of the 31 RNA modifications showed marked variations during tumorigenesis. Eight RNA modifications (m2,2G, t6A, m7G, m5U, m1G, i6A, m6t6A and m1A), which were upregulated in ovarian cancer tissues and in RMG-1-xenografted tumour, were also upregulated under hypoxic conditions. RNAseq analysis, using the matched RNA samples analysed for RNA modifications, showed that 2137 genes were highly expressed in ovarian cancer tissues compared with those in normal ovarian tissues. Of these, 134 genes, which were enriched in a gene set belonging to the hypoxia signalling pathway, were positively correlated with the above eight RNA modifications. These results suggest that the tumour microenvironment, including hypoxia, is important for cancer characteristic RNA modifications.


Asunto(s)
Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , ARN , Hipoxia/genética , Microambiente Tumoral/genética
10.
Ann Surg ; 278(4): e805-e811, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36398656

RESUMEN

OBJECTIVE: This study aimed to compare the short-term outcomes between laparoscopic and open distal pancreatectomy for lesions of the distal pancreas from a real-world database. BACKGROUND: Reports on the benefits of laparoscopic distal pancreatectomy include 2 randomized controlled trials; however, large-scale, real-world data are scarce. METHODS: We analyzed the data of patients undergoing laparoscopic or open distal pancreatectomy for benign or malignant pancreatic tumors from April 2008 to May 2020 from a Japanese nationwide inpatient database. We performed propensity score analyses to compare the inhospital mortality, morbidity, readmission rate, reoperation rate, length of postoperative stay, and medical cost between the 2 groups. RESULTS: From 5502 eligible patients, we created a pseudopopulation of patients undergoing laparoscopic and open distal pancreatectomy using inverse probability of treatment weighting. Laparoscopic distal pancreatectomy was associated with lower inhospital mortality during the period of admission (0.0% vs 0.7%, P <0.001) and within 30 days (0.0% vs 0.2%, P =0.001), incidence of reoperation during the period of admission (0.7% vs 1.7%, P =0.018), postpancreatectomy hemorrhage (0.4% vs 2.0%, P <0.001), ileus (1.1% vs 2.8%, P =0.007), and shorter postoperative length of stay (17 vs 20 d, P <0.001). CONCLUSIONS: The propensity score analysis revealed that laparoscopic distal pancreatectomy was associated with better outcomes than open surgery in terms of inhospital mortality, reoperation rate, postoperative length of stay, and incidence of postoperative complications such as postpancreatectomy hemorrhage and ileus.


Asunto(s)
Ileus , Obstrucción Intestinal , Laparoscopía , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Pancreatectomía , Puntaje de Propensión , Resultado del Tratamiento , Tiempo de Internación , Obstrucción Intestinal/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía
11.
Mol Ther Nucleic Acids ; 34: 102079, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38213952

RESUMEN

Replenishing tumor-suppressor miRNAs (TS-miRNAs) is a potential next-generation nucleic acid-based therapeutic approach. Establishing an effective miRNA delivery system is essential to successful TS-miRNA therapy. To overcome vulnerability to RNA nucleases, we previously developed a chemically modified miRNA143-3p (CM-miR-143). In clinical practice, colorectal cancer (CRC) pelvic recurrence is an occasional challenge following curative resection, requiring a novel therapy because reoperative surgery poses a significant burden to the patient. Hence, we considered the use of CM-miR-143 as an alternative treatment. In this study, we used a mouse model bearing pelvic CRC adjacent to the rectum and investigated the anticancer effects of CM-miR-143 lipoplexes formulated from miRNA and a cationic liposome. Compared with commercial synthetic miR-143, CM-miR-143 lipoplexes accumulated heavily in regions of the pelvic CRC tumor where the blood flow was high. As a result, systemic administration of CM-miR-143 lipoplexes improved animal survival by significantly suppressing pelvic CRC tumors and relieving a lethal bowel obstruction caused by rectal compression. Detailed protein analysis revealed that the myristoylated alanine-rich C kinase is a novel target for CM-miR-143 lipoplexes. Our results suggest that CM-miR-143 is a potential next-generation drug candidate in the treatment of CRC pelvic recurrence.

12.
Int J Mol Sci ; 23(24)2022 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-36555361

RESUMEN

Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC.


Asunto(s)
Adenocarcinoma de Células Claras , Vesículas Extracelulares , MicroARNs , Neoplasias Ováricas , Femenino , Humanos , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/genética , Biomarcadores , Vesículas Extracelulares/genética , MicroARNs/genética , Ovario , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética
13.
J Clin Med ; 11(24)2022 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-36556119

RESUMEN

This study aimed to identify factors predicting the probability of serious fetal acidemia at delivery in placental abruption. We identified 5769 women who delivered at >22 weeks' gestation at two institutions in a tertiary referral unit specializing in neonatal infant care between January 2007 and December 2011. Ninety-one abruption cases were identified based on clinical and histological diagnoses. Serious fetal acidemia was defined as a pH < 7.0 in the umbilical arterial blood at delivery. Using a linear discriminant function, we calculated the score to determine the probability of serious fetal acidemia. Serious fetal acidemia was observed in 34 patients (37.4%). A logistic regression model showed that abnormal fetal heart rate patterns (bradycardia and late decelerations), uterine spasm, and maternal plasma concentration of fibrinogen less than 288 ng/dL were significantly associated with the occurrence of serious fetal acidemia. We suggest that the implementation of maternal fibrinogen in patients with placental abruption is a prognostic factor for serious fetal acidemia at delivery.

14.
Case Rep Obstet Gynecol ; 2022: 5612091, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36046125

RESUMEN

The use of heparin and low-dose aspirin is the current conventional treatment for pregnant females with antiphospholipid syndrome (APS). However, there is no additional treatment recommended for cases where the standard treatment cannot prevent obstetric complications such as fetal loss and placental insufficiency. Recently, the addition of a novel antimalarial, hydroxychloroquine (HCQ), to the conventional treatment has shown the potential to prevent obstetric complications. Herein, we report a case in which the addition of HCQ improved adverse pregnancy outcomes in a pregnant female with systemic lupus erythematosus and aspirin-heparin-resistant APS.

15.
Int J Med Robot ; 18(6): e2451, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35960009

RESUMEN

BACKGROUND: The sentinel lymph node (SLN) procedures using indocyanine green (ICG) have recently been performed worldwide. The aim of this study was to emphasise the safety of robot-assisted modified radical hysterectomy (RAMRH) with removal of the lymphatic vessels (RLV) using ICG in endometrial cancer according to a single surgeon's experience. METHODS: Robot-assisted modified radical hysterectomy with RLV using ICG was performed in patients with endometrial cancer. We compared 34 cases of RAMRH with RLV, with 54 patients without RLV. RESULTS: The median (interquartile range) time for the procedure did not differ between the RAMRH with and without RLV groups (88 [80-114] vs. 88 [79-104] min, p = 0.7). The success rate of RLV was 100% when SLNs were detected. CONCLUSION: Robot-assisted modified radical hysterectomy with RLV using ICG can completely dissect tissue from the uterus, including lymphatic vessels. This procedure using a robotic system with ICG, is simple and does not require additional time.


Asunto(s)
Neoplasias Endometriales , Vasos Linfáticos , Robótica , Femenino , Humanos , Verde de Indocianina , Biopsia del Ganglio Linfático Centinela/métodos , Colorantes , Histerectomía/métodos , Neoplasias Endometriales/cirugía , Vasos Linfáticos/patología
16.
J Obstet Gynaecol Res ; 48(11): 2863-2871, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35934761

RESUMEN

AIM: To evaluate the impact on urodynamic results between the laparoscopic nerve-sparing radical hysterectomy (LRH) following a step-by-step procedure and abdominal nerve-sparing radical hysterectomy (ARH) for patients with uterine cervical cancer. METHODS: This retrospective study enrolled 76 patients with cervical cancer: 35 in the LRH group and 41 in the ARH group. We analyzed their postoperative bladder function in a urodynamics study and examined the volume of resected pelvic nerves contained in parametrial sections using S-100 antibody staining. RESULTS: Estimated blood loss and hospital stay after operation for the LRH group were significantly better than those in the ARH group (p < 0.0001). As well, the number of harvested lymph nodes was significantly higher in the LRH group (p = 0.044). There was no difference in perioperative complications between the two groups in this study. The 5-year disease-free survival rates and overall survival rates were 91.2% and 94.0% in the LRH group and 87.8% and 95.1% in the ARH group, both respectively. Although the median residual urine volume were no statistical differences between the LRH group and the ARH group, the recovery of postoperative bladder function (uroflowmetry) in the LRH group rapidly reached presurgery levels at 1 month, and the LRH group had a smaller number of s-100 antibody stained nerves contained the parametrial sections. CONCLUSION: We demonstrated that LRH following a step-by-step procedure could achieve a higher level of prevention of damage to the bladder branch of the pelvic splanchnic nerve plexus and thus restore bladder function more rapidly.


Asunto(s)
Laparoscopía , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/patología , Urodinámica , Estudios Retrospectivos , Laparoscopía/métodos , Estadificación de Neoplasias , Resultado del Tratamiento , Histerectomía/métodos
17.
Cancers (Basel) ; 14(12)2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35740635

RESUMEN

Patient-derived xenograft (PDX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies, and can be developed by the heterotopic or orthotopic grafting of surgically resected tumors into immunodeficient mice. We report the PDX models of cervical cancer and demonstrate the similarities among original and different generations of PDX tumors. Fresh tumor tissues collected from 22 patients with primary cervical cancer were engrafted subcutaneously into NOD.CB17-PrkdcSCID/J mice. Histological and immunohistochemical analyses were performed to compare primary and different generations of PDX tumors. DNA and RNA sequencing were performed to verify the similarity between the genetic profiles of primary and PDX tumors. Total RNA in extracellular vesicles (EVs) released from primary and PDX tumors was also quantified to evaluate gene expression. The total tumor engraftment rate was 50%. Histologically, no major differences were observed between the original and PDX tumors. Most of the gene mutations and expression patterns related to carcinogenesis and infiltration were similar between the primary tumor and xenograft. Most genes associated with carcinogenesis and infiltration showed similar expression levels in the primary tumor and xenograft EVs. Therefore, compared with primary tumors, PDX models could be potentially more useful for translational research.

18.
J Clin Med ; 11(9)2022 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-35566732

RESUMEN

BACKGROUND: Because patient-derived xenograft (PDX) models resemble the original tumors, they can be used as platforms to find target agents for precision medicine and to study characteristics of tumor biology such as clonal evolution and microenvironment interactions. The aim of this review was to identify articles on endometrial cancer PDXs (EC-PDXs) and verify the methodology and outcomes. METHODS: We used PubMed to research and identify articles on EC-PDX. The data were analyzed descriptively. RESULTS: Post literature review, eight studies were selected for the systematic review. Eighty-five EC-PDXs were established from 173 patients with EC, with a total success rate of 49.1%. A 1-10 mm3 fragment was usually implanted. Fresh-fragment implantation had higher success rates than using overnight-stored or frozen fragments. Primary tumors were successfully established with subcutaneous implantation, but metastasis rarely occurred; orthotopic implantation via minced tumor cell injection was better for metastatic models. The success rate did not correspond to immunodeficiency grades, and PDXs using nude mice reduced costs. The tumor growth period ranged from 2 weeks to 13 months. Similar characteristics were observed between primary tumors and PDXs, including pathological findings, gene mutations, and gene expression. CONCLUSION: EC-PDXs are promising tools for translational research because they closely resemble the features of tumors in patients and retain molecular and histological features of the disease.

19.
Curr Oncol ; 29(4): 2272-2283, 2022 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-35448159

RESUMEN

Minimally invasive surgery (MIS) is performed to treat cervical cancer patients; however, a recent study showed that MIS was associated with higher recurrence and death rate compared with abdominal radical hysterectomy (ARH). In the current study, the prognosis of patients with early-stage cervical cancer who underwent MIS with vaginal closure or ARH was evaluated. One hundred and eighty-two patients underwent radical hysterectomy for cervical cancer with stage of IA2, IB1, and IIA1. MIS was performed by laparoscopy or a robot using the vaginal closure method. Disease-free survival (DFS) and overall survival (OS) were evaluated between the groups. Among the patients, 67 underwent MIS and 115 underwent ARH. The recurrence rate was 4.5% in MIS patients and 3.5% in ARH patients with a median follow-up (interquartile range) of 36 (18-60) and 78 (48-102) months, respectively. DFS and OS were not different between the groups (3y-DFS, 95.3% vs. 96.1%, p = 0.6; 3y-OS, 100% vs. 100%, p = 0.06). In early-stage cervical cancer patients, MIS with vaginal closure did not increase the risk for recurrence or death. Surgical techniques and procedures to avoid spillage of tumor cells could be important for a better prognosis.


Asunto(s)
Neoplasias del Cuello Uterino , Femenino , Humanos , Histerectomía/métodos , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía
20.
Int J Clin Oncol ; 27(6): 1084-1092, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35287187

RESUMEN

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.


Asunto(s)
Neoplasias Endometriales , Histerectomía , Anciano , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía/métodos , Japón , Escisión del Ganglio Linfático/métodos , Estadificación de Neoplasias , Estudios Retrospectivos
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