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Recent studies show increased expression of human epidermal growth factor receptor 2 (HER2) in cervical cancer, but the efficacy of anti-HER2 therapy remains under-researched. Here, we present a case of recurrent HER2-positive serous carcinoma, presumably arising in the cervix, diagnosed by comprehensive genomic profiling, which responded to trastuzumab. The patient underwent a radical hysterectomy with concurrent adjuvant chemoradiotherapy. One year after surgery, the patient experienced recurrence (multiple lymph node metastases). She underwent chemotherapy and subsequent comprehensive genomic profiling, which revealed HER2 positivity. Despite treatment, the lymph node and peritoneal metastases progressed. Therefore, combination chemotherapy with paclitaxel and trastuzumab was initiated. Subsequently, the patient's clinical symptoms improved considerably, and good health was maintained for 8 months. This report highlights the importance of comprehensive genomic profiling and targeted therapies when standard treatments fail.
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Endometrial cancer (EC) in women is increasing globally, necessitating improved diagnostic methods and prognosis prediction. While endometrial histology is the conventional approach, liquid-based endometrial cytology may benefit from novel analytical techniques for cell clusters. A clinical study was conducted at the University of Fukui Hospital from 2012 to 2018, involving 210 patients with endometrial cytology. The liquid-based cytology images were analyzed using cell cluster analysis with Image J software. Logistic regression, ROC analysis, and survival analysis were employed to assess the diagnostic accuracy and prognosis between cell cluster analysis and EC/atypical endometrial hyperplasia (AEH). Circularity and fractal dimension demonstrated significant associations with EC and AEH, regardless of age and cytology results. The ROC analysis revealed improved diagnostic accuracy when combining fractal dimension with cytology, particularly in menopausal age groups. Lower circularity and solidity were independently associated with poor overall survival, while higher fractal dimension values correlated with poorer overall survival in Grades 2 and 3 endometrial cancers. The combination of circularity and fractal dimension with cytology improved diagnostic accuracy for both EC and AEH. Moreover, circularity, solidity, and fractal dimension may serve as prognostic indicators for endometrial cancer, contributing to the development of more refined screening and diagnostic strategies.
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Background and Objective: In endometrial cytology, differentiating endometrial glandular stromal breakdown (EGBD) from endometrial endometrioid carcinoma (G1-EEC) is often difficult. In this study, we provided a new focus on chondroitin sulfate (CS), a major substrate component of the endometrial stroma, and assessed the diagnostic utility of Alcian Blue (AB) staining in the differential diagnosis in liquid-based cytological (LBC) samples. Materials and Methods: LBC specimens from 19 patients with a proliferative endometrium, 36 with EGBD, and 30 with G1-EEC who underwent endometrial cytology were stained with AB (pH 1.0), and their reactivity was observed. In addition, immunocytochemical staining of CS and CD31 was performed for five cases each to evaluate their interrelationship with blood vessels. Results: Regarding the 30 G1-EEC cases, at least one of the three representative staining patterns was observed by AB staining: dot-like, microtubular, and finely branched linear patterns. Moreover, the inner portion of the tubular material observed by AB staining expressed CD31. Conversely, in the 36 EGBD cases, only five metaplastic clusters with irregular protrusions and condensed stromal clusters (CSCs) showed a dot-like positive pattern, and background CSCs did not show reactivity to AB staining in any of the cases. Furthermore, the vascular structure expressing CD31 in cell clusters was also unclear. Conclusions: We demonstrated that AB staining shows different staining patterns in G1-EEC and EGBD, reflecting their different tissue structures. Our data provide new insights into endometrial cell diagnosis changes and demonstrate that AB staining is a potential new diagnostic aid tool for the differentiation of G1-EEC from EGBD.
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INTRODUCTION: This study aimed to assess the localization of chondroitin sulfate (CS), a primary extracellular matrix component, in the stromal region of endometrial carcinoma (EC). METHODS: Immunostaining was performed on 26 endometrial endometrioid carcinoma (EEC) samples of different grades and 10 endometrial serous carcinoma (ESC) samples to evaluate CS localization. This was further confirmed by Alcian Blue (AB) staining as well. RESULTS: In the G1-EEC samples, CS showed reactivity with fibrovascular stroma, supporting closely packed glandular crowding and papillary structures. As the grade increased, the original interstitial structure was re-established, and the localization of CS in the perigulandular region decreased. In the ESC samples, the thick fibrous strands supporting the papillary architecture showed reactivity with CS; however, the delicate stromal region branching into the narrow region showed poor reactivity. The AB staining results showed similar characteristics to the immunostaining ones. CONCLUSIONS: The characteristic localization of CS in various EC types was elucidated. The present study provides new information on endometrial stromal assessment.
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Sulfatos de Condroitina , Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/diagnóstico , Sulfatos de Condroitina/metabolismo , Sulfatos de Condroitina/análise , Pessoa de Meia-Idade , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/metabolismo , Idoso , Imuno-HistoquímicaRESUMO
A human ovarian clear cell carcinoma cell line was established from a 46-year-old Japanese woman. That line, designated MTC-22, has proliferated continuously for over 6 months in conventional RPMI 1640 medium supplemented with 10% foetal bovine serum and has been passaged over 50 times. MTC-22 doubling-time is ~ 18 h, which is much shorter than most ovarian clear cell carcinoma lines reported to date. Morphologically, MTC-22 cells exhibit polygonal shapes and proliferate to form a monolayer in a jigsaw puzzle-like arrangement without contact inhibition. Ultrastructurally, cells exhibit numerous intracytoplasmic glycogen granules and well-developed mitochondria. G-band karyotype analysis indicated that cells have a complex karyotype close to tetraploid. We observed that the expression pattern of a series of ovarian carcinoma-related molecules in MTC-22 cells was identical to that seen in the patient's tumour tissue. Notably, MTC-22 cells, and the patient's carcinoma tissue, expressed low-sulphated keratan sulphate recognised by R-10G and 294-1B1 monoclonal antibodies, a hallmark of non-mucinous ovarian carcinoma, and particularly of clear cell ovarian carcinoma. Moreover, characteristic point mutations-one in ARID1A, which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase-were seen in the patient's tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.
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Adenocarcinoma de Células Claras , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Linhagem Celular Tumoral , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Pessoa de Meia-Idade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Mutação/genética , Mutação Puntual/genética , Proliferação de Células/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genéticaRESUMO
Cervical cancer incidence is increasing among Japanese women, which is partly attributed to low screening rates. This study examined the implementation of opt-in human papillomavirus (HPV) self-sampling among Japanese women aged 30-39 years who had not undergone cervical cancer screening, focusing on those requiring preconception care. The responses to the opt-in approach and effectiveness in detecting cervical squamous intraepithelial neoplasia 2 or worse (CIN2+) were evaluated. Participants used the Evalyn® Brush for self-sampling, with HPV testing conducted using the Cobas 4800 system (version 2.2.0). Out of 3489 eligible, unscreened women from four municipalities in Fukui Prefecture, only 10.6% (370/3489) requested the self-sampling kit. Of these, 77.3% (286/370) returned the kit (HPV testing rate: 8.2% (286/3489)). The HPV positivity rate was 13.7% (39/285), yet only 61.5% (24/39) of those with positive HPV results proceeded to cytology testing. Subsequently, three cases of CIN2+ were detected (10.5/1000). While this study demonstrated a reasonable kit return rate and indicated the capability of opt-in HPV self-sampling to detect CIN2+ cases in unscreened women, the low ordering rate of kits and suboptimal compliance for follow-up cytology testing highlight significant challenges. The findings suggest the need for more effective strategies to enhance participation in cervical cancer screening programs.
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BACKGROUND: Placenta accreta spectrum (PAS) cesarean hysterectomy is performed under conditions of shock and can result in serious complications. This study aimed to evaluate the usefulness of the "Holding-up uterus" surgical technique with a shock index (S.I.) > 1.5. METHODS: Twelve patients who underwent PAS cesarean hysterectomy were included in the study. RESULTS: Group I had S.I. > 1.5, and group II had S.I. ≤ 1.5. Group I had more complications, but none were above Grade 3 or fatal. Preoperative scheduled uterine artery embolization did not result in serious complications, but three patients who had emergency common iliac artery balloon occlusion (CIABO) and a primary total hysterectomy with S.I. > 1.5 had postoperative Grade 2 thrombosis. Two patients underwent manual ablation of the placenta under CIABO to preserve the uterus, both with S.I. > 1.5. CONCLUSIONS: The study found that the "Holding-up uterus" technique was safe, even in critical situations with S.I. > 1.5. CIABO had no intervention effect. The study also identified assisted reproductive technology pregnancies with a uterine cavity length of less than 5 cm before conception as a critical factor.
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Oclusão com Balão , Placenta Acreta , Gravidez , Feminino , Humanos , Placenta Acreta/cirurgia , Placenta Acreta/etiologia , Perda Sanguínea Cirúrgica , Oclusão com Balão/métodos , Artéria Ilíaca , Útero/cirurgia , Histerectomia/métodos , Estudos RetrospectivosRESUMO
The coronavirus disease (COVID-19) pandemic has raised concerns about the impact of delayed health check-ups and cancer screenings on cancer diagnosis and treatment. This study aimed to investigate the awareness of cancer patients on future screening measures during the pandemic in rural Japan. An anonymized open-data survey was undertaken in Fukui Prefecture, a rural region of Japan, in 2021. Participants were asked about their cancer screening history, screening frequency during the pandemic, and reasons for not undergoing screening. Among the 1262 respondents, the proportion of patients who underwent cancer screening in 2020 during the pandemic was similar to the proportion who underwent regular (annual or biannual) screening in 2019 before the pandemic. Of those who underwent regular screening, 82% still underwent screening in 2020, while only 21% of those who had irregular screenings. The number of respondents who believed they were healthy and did not require screening increased over time, possibly due to restrictions on going out and refraining from activities during the pandemic. This study in rural Japan found that regular cancer screening prior to the pandemic was associated with a more positive attitude toward screening during the pandemic. Raising awareness about the importance of cancer screening and encouraging participation is crucial for promoting positive attitudes in the future. The findings highlight the need for continued efforts to ensure access to screening services during the pandemic and future public health emergencies.
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COVID-19 , Neoplasias , Humanos , Pandemias , Detecção Precoce de Câncer , Japão/epidemiologia , COVID-19/epidemiologia , Inquéritos e Questionários , Neoplasias/diagnóstico , Neoplasias/epidemiologiaRESUMO
INTRODUCTION: The objective of this study was to assess the diagnostic utility of CD10 in the differential diagnosis of grade 1-endometrial endometrioid carcinoma (G1-EEC) and the metaplastic changes associated with the endometrial glandular and stromal breakdown (EGBD) on liquid-based cytological (LBC) samples. METHODS: (1) The type and distribution of CD10-positive cells in EGBD and G1-EEC patients were evaluated. (2) Based on the results from (1), histological and cytological specimens were double-immunostained with CD31 and CD10 to confirm whether CD10-positive tubular-canalicular material found in (1) was represented by fine threads of endometrial-type fibrovascular stroma. (3) Based on the results from (2), additional immunostaining of histological specimens was performed for CD146 and αSMA as markers of perivascular cells. RESULTS: (1) CD10 positive cells showed two main patterns of expression: cytoplasmic immunoreactivity in the form of dense brown granules in EGBD and tubular-canalicular branching patterns in G1-EEC. (2) The tubular-canalicular material observed in cytological specimens of G1-EEC samples co-expressed CD10 and CD31, and was interpreted as representing fine threads of endometrial fibrovascular stroma in the corresponding histological samples. Conversely, metaplastic changes in EGBD cases, only a few CD31-positive signals were found inside the condensed stromal clusters with CD10-positive. (3) Cells surrounding the CD31-positive vascular endothelial cells expressed CD146 and αSMA; moreover, some of the thin CD10-positive fibrous stromal strands also co-expressed αSMA. CONCLUSIONS: CD10 is a very useful immunomarker for distinguishing between G1-EEC and the metaplastic changes of EGBD in LBC samples.
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Carcinoma Endometrioide , Neoplasias do Endométrio , Antígeno CD146/metabolismo , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Humanos , Neprilisina/metabolismo , Molécula-1 de Adesão Celular Endotelial a PlaquetasRESUMO
BACKGROUND: In general, human papillomavirus (HPV) vaccines have demonstrated efficacy in young women worldwide, but there is limited evidence on the efficacy of the quadrivalent HPV6/11/16/18 vaccine in adult women and no evidence of its effectiveness in Japanese adult women in particular. This study aims to evaluate the efficacy of the quadrivalent HPV6/11/16/18 vaccine for persistent HPV16/18 infection in Japanese women aged 27-45 years. METHODS: This is an interventional, nonrandomized, non-double-blind prospective cohort study designed to compare the rates of persistent HPV16/18 infection between the vaccinated arm and unvaccinated arm. The subjects will consist of all women aged 27-45 years who have normal cytology results confirmed by cervical cancer screening from May 2019 to March 2021. The follow-up time is two years. The subjects will be divided into two groups: the vaccinated group and the unvaccinated group. The study will need to enroll 600 vaccinated participants (experimental arm) and 2200 unvaccinated participants (control arm). DISCUSSION: The findings of this trial (HAKUOH study) might provide the first local evidence on the subject and be significantly useful not only to medical academia but also to the Japanese Ministry of Health, Labour and Welfare. The findings could contribute to public health improvement by providing local supportive knowledge on the prevention of HPV infection through HPV vaccination in young adult women in Japan, where active recommendations have been suspended for a long time due to adverse effects. TRIAL REGISTRATION: Trial registration number: NCT04022148 . Registration began on December 1, 2019.
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Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Adulto , Diagnóstico Precoce , Feminino , Seguimentos , Voluntários Saudáveis , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/farmacologia , Papillomavirus Humano 16/efeitos dos fármacos , Papillomavirus Humano 18/efeitos dos fármacos , Humanos , Japão , Infecções por Papillomavirus/prevenção & controle , Estudos Prospectivos , Projetos de PesquisaRESUMO
BACKGROUND: To adopt HPV self-sampling in Japan, we assessed the concordance between self- and physician-collected human papillomavirus (HPV) samples from Japanese patients and examined the performance of HPV self-sampling for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: Patients who had previously tested negative for intraepithelial lesions or malignancy/HPV-positive, and patients with atypical squamous cells of undetermined significance or worse (ASCUS+) cytology were eligible for this cross-sectional study. Participants performed HPV self-sampling using an Evalyn brush, which was submitted at the Fukui Prefectural Health Care Association. The Evalyn brush heads were stored in ThinPrep vials. The physician, however, performed HPV and cell sampling using an endocervical brush and immediately stored the brush heads in ThinPrep vials. All participants underwent colposcopy and biopsy. Histopathological diagnoses were made by pathologists at Fukui University Hospital. HPV infection was confirmed using a PCR-based Cobas 4800 HPV DNA test. Cytological analysis was performed at Fukui Prefectural Health Care Association. RESULTS: HPV-positive rates for physician-collected samples and self-collected samples were 51 and 50%, respectively. The perfect match rate of HPV type between the groups was 88% (κ = 0.76). HPV16/18 showed higher agreement rates than other HPVs (99%, kappa 0.96 and 89% kappa 0.77, respectively). Both groups showed 100% sensitivity to CIN2+, but specificity was 57.0 and 58.1%, respectively. CONCLUSION: For HPV typing, a good concordance rate was seen between self- and physician-collected samples. Self-sampling showed high sensitivity for CIN2+. Self-sampling using the Evalyn brush and Cobas 4800 may be feasible for screening Japanese individuals.
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Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Autocuidado/instrumentação , Manejo de Espécimes/instrumentação , Manejo de Espécimes/métodos , Adulto , Povo Asiático , Células Escamosas Atípicas do Colo do Útero/patologia , Células Escamosas Atípicas do Colo do Útero/virologia , Colposcopia , Estudos Transversais , Feminino , Testes de DNA para Papilomavírus Humano , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Médicos , Reação em Cadeia da Polimerase , Autocuidado/métodos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: The introduction and establishment of a new classification system for endometrial cytology, the "New Terminology in Endometrial Cytology (NTEMC) system," which is based on the Bethesda System for uterine cervical cytology, has recently been reported. However, the clinical management for new categories in the NTEMC system, particularly atypical endometrial cells (ATEC), has not been clarified. The objective of the present study is to determine how the ATEC category should be treated and whether the introduction of the system has decreased the number of unnecessary endometrial biopsies. METHODS: Fifty-nine cases were diagnosed as "suspicious positive" according to the three-tier reporting (TTR) system, which was adopted in Japan. The specimens were re-evaluated according to the NTEMC system. Thirty-seven of the 59 patients underwent endometrial biopsy. We correlated the pathological diagnosis with the NTEMC system category. RESULTS: The 59 cases were classified according to the NTEMC system as follows: 36 cases were classified as ATEC of undetermined significance (ATEC-US), 21 cases were classified as ATEC for which atypical endometrial hyperplasia or worse cannot be excluded (ATEC-A), and 2 cases were classified as endometrial hyperplasia. The ratio of atypical endometrial hyperplasia or malignancy in ATEC-US category was significantly lower than that in ATEC-A category. Fifteen cases in ATEC-US category did not show atypical endometrial hyperplasia lesions or malignancy after 3 months. CONCLUSIONS: These data suggest that patients with ATEC-US results can be followed up for at least three months, and the introduction of the NTEMC system decreased the number of unnecessary endometrial biopsies.
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Carcinoma/classificação , Neoplasias do Endométrio/classificação , Prontuários Médicos/normas , Terminologia como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The aim of this study was to determine whether a preoperative health status index and intraoperative data could predict perioperative morbidity and mortality in women over the age of 65 years undergoing surgery for gynecologic disorders. METHODS: The medical records of 68 female patients who were ≥65 years of age and who underwent surgery under general anesthesia in our institute from January 2014 to December 2015 were retrospectively reviewed. Preoperative data were extracted from a database and included comorbidities, American Society of Anesthesiologists physiological status classification, the Charlson Comorbidity Index, the Subjective Global Assessment 2011 revision, the subjects' risk of falling, body mass index, and age. The intraoperative factors investigated included the type of surgery and the Surgical Apgar Score (SAS). Major postoperative complications were defined as > Grade 3 based on the Clavien-Dindo classification version 2.0. RESULTS: Of the 68 elderly gynecological patients, 6 (8.8%) developed serious Grade 3 or worse complications within 30 days of surgery. The only factor that significantly affected postoperative complications was the SAS, an index of the patient's intraoperative condition. The optimum cut-off SAS for the occurrence of complications was determined by the receiver operating characteristic curve to be ≤ 6 points; a score ≤6 points predicted the development of postoperative complications with 66.7% sensitivity and 79.0% specificity. CONCLUSION: In this study, the SAS predicted the development of serious complications in elderly gynecological patients within 30 days of surgery more accurately than did other comorbidities, preoperative assessments, and type of surgery.
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Técnicas de Apoio para a Decisão , Procedimentos Cirúrgicos em Ginecologia , Indicadores Básicos de Saúde , Complicações Pós-Operatórias , Idoso , Feminino , Humanos , Estudos RetrospectivosRESUMO
We investigated whether 16α-[18F]-fluoro-17ß-estradiol (18F-FES) and 18F-fluoro-deoxyglucose (FDG) uptake measured using positron emission tomography (PET) predicted prognosis in 18 patients with different histological subtypes of uterine sarcoma. Standardized uptake values (SUVs) and 18F-FDG/18F-FES SUV ratios were determined, and their correlations with progression-free (PFS) and overall survival (OS) were examined. Ten patients died from local recurrence or metastasis, and one more experienced recurrence, during the at least 36-month follow-up period. Patients with higher 18F-FDG SUVs (> 5.5) had worse OS (p = 0.007) and tended toward worse PFS (p = 0.11), while patients with lower 18F-FES SUVs (≤ 1.5) had worse PFS (p = 0.03) and tended toward worse OS (p = 0.19). Patients with 18F-FDG/18F-FES ratios > 2.6 had worse PFS (p = 0.009) and OS (p = 0.005). The 5-year PFS and OS rates were 75% and 88% for patients with lower ratios, but were only 10% and 20% for those with higher ratios. These results suggest that pretreatment tumor 18F-FDG/18F-FES ratio is useful for predicting the prognosis of uterine sarcoma patients.
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Estradiol/análogos & derivados , Fluordesoxiglucose F18/metabolismo , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Sarcoma/diagnóstico por imagem , Neoplasias Uterinas/diagnóstico por imagem , Estradiol/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Compostos Radiofarmacêuticos/metabolismo , Sarcoma/metabolismo , Sarcoma/patologia , Taxa de Sobrevida , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologiaRESUMO
This study aimed to investigate whether the predictive values of intensity- and volume-based PET parameters are different between histological subtypes in patients with cervical cancer. Ninety patients, 65 with squamous cell carcinoma (SCC) and 25 with non-SCC (NSCC), who underwent pretreatment ¹8F-FDG PET/CT and pelvic MRI, were studied retrospectively. In addition to SUVmax and SUVmean, metabolic-tumor-volume (MTV) was determined by thresholding of 40% SUVmax and total-lesion-glycolysis (TLG) was calculated. Clinical factors and PET metabolic indices were compared between SCC and NSCC. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method with cut-offs determined by ROC analyses to stratify SCC and NSCC patients separately. Factors associated with survival were assessed with univariate and multivariate analyses using the Cox regression model. No significant differences were observed in clinical factors other than tumor size or ¹8F-FDG PET metabolic indices between SCC and NSCC. The Kaplan-Meier estimates of 2-year PFS and OS rates were 60% and 70% for SCC and 40% and 76% for NSCC, respectively. Multivariate analyses showed that MTV and TLG were the independent prognostic factors for PFS and OS in SCC; in contrast, SUVmax was the independent prognostic factor for PFS and OS in NSCC. Metabolic burden (MTV and TLG) could be beneficial for the prognostic prediction of cervical SCC patients; in contrast, metabolic intensity (SUVmax) could be beneficial for the prognostic prediction of NSCC patients. The different prognostic implications might be based on the differences of tissue integrity and histological heterogeneity between SCC and NSCC.
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Carcinoma de Células Escamosas/diagnóstico , Fluordesoxiglucose F18 , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidadeRESUMO
Both ligand-dependent and ligand-independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation and results in activation of the ERα-dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is also known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and MAPK/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated-ERα at Ser(167) (p-Ser(167) -ERα). However, the expression of p-Ser(167) -ERα in EEC and its prognostic role in ECC is largely unexplored. The purpose of the present study was to investigate the expression of p-Ser(167) -ERα in ECC and its relationship with prognosis. Immunohistochemical staining of primary EEC surgical specimens (n = 103) was carried out using antibodies specific for p-Ser(167) -ERα and for p-mTOR/p-S6K1 and p-MAPK/p-RSK. The correlation of p-Ser(167) -ERα expression with clinicopathological features and survival of ECC was studied. Patients that were positive for nuclear p-Ser(167) -ERα had significantly shorter relapse-free survival, and although the result was not significant, levels of nuclear p-Ser(167) -ERα tended to be higher in advanced-stage ECC patients. Nuclear p-Ser(167) -ERα was significantly positively correlated with p-MAPK and p-S6K1, and with significantly shorter relapse-free survival in EEC.
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Carcinoma Endometrioide/metabolismo , Neoplasias do Endométrio/metabolismo , Receptor alfa de Estrogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/mortalidade , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Advanced uterine leiomyosarcoma (LMS) is a rare and extremely aggressive disease. In patients with advanced and unresected uterine LMS, multidisciplinary therapy is the best treatment option, although no consensus exists on the efficacy of the treatment. The present study describes the case of a 41-year-old female who underwent laparotomy due to a large uterine tumor. Exploratory laparotomy revealed a large tumor that had extended from the pelvic wall to the outside of the pelvis and then invaded the colon. Large residual tumors remained present in the pelvis following suboptimal debulking surgery. Subsequent to surgery, the patient was treated with adjuvant radiotherapy, followed by chemotherapy with regional whole pelvis hyperthermia (HT). Computed tomography revealed stable disease prior and subsequent to combination treatment. While treatment was being administered for third/fourth-degree burns and subcutaneous fatty necrosis, the patient developed multi-organ failure and succumbed. The present case report describes the potential for using a combination of chemotherapy, HT and radiotherapy in patients with LMS. The development of an effective protocol is required for the administration of chemotherapy, HT and radiotherapy in patients with advanced unresected LMS.
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Cisplatin is one of the most potent antitumor agents for ovarian cancer, but has also been implicated in normal tissue cytotoxicity. We examined the effect of cisplatin alone and in combination with C16Y, a newly-identified anti-angiogenic peptide from the NH2-terminal domains of the γ-chain of laminin-1, on the modulation of Bcl-2/Bax expression and induction of apoptosis in ovarian cancer cells (OVACAR3). C16Y did not elicit cell death of human umbilical vein endothelial cells (HUVECs). Cisplatin exerted a lethal effect with an EC50 of 10 µM in OVACAR3s. In the presence of 25 or 50 µg/ml of C16Y (a range which has no effect against HUVECs), the EC50 for cisplatin in OVACAR3s decreased to 3.5 and 2.0 µM, respectively. Using fluorescence-activated cell sorting (FACS) analysis of DNA stained OVACAR3s and terminal deoxynucleotide tranferase-mediated dUTP nick end-labeling (TUNEL), we found that even at concentrations of 1 and 3 µM cisplatin, C16Y at 10 and 25 µg/ml increased the incidence of apoptosis in OVACAR3s by 3-5-fold. Each drug had some measurable effect on Bax protein expression. Furthermore, Bcl-2 protein expression levels were markedly reduced by C16Y alone and cisplatin alone in a dose-dependent manner. The combination of C16Y and cisplatin resulted in a further dramatic reduction in Bcl-2, underscoring the pronounced synergy produced by cisplatin and C16Y together. On the other hand, C16Y did not activate any other signal transduction pathways that usually culminate in the activation of apoptosis, such as the p53, p21waf1, p73, ERK1/2 or PI3-AKT pathways. These observations suggest that the suppression of the Bcl-2/Bax ratio may play an important role in mediating the synergistic effect of cisplatin and C16Y on the induction of apoptosis in OVACAR3 cells.
Assuntos
Inibidores da Angiogênese/farmacologia , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Oligopeptídeos/farmacologia , Neoplasias Ovarianas/metabolismo , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Células Endoteliais/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Células NIH 3T3 , Neoplasias Ovarianas/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To report 2 cases of a probable interaction between cisplatin and warfarin. CASE SUMMARY: Two cases of transient elevation of international normalized ratio (INR) during irinotecan (60 mg/m2 on days 1, 8, and 15) plus cisplatin (60 mg/m2 on day 1) chemotherapy with concomitant warfarin are presented. In both cases, warfarin dosages were stable at the therapeutic target range prior to initiation of chemotherapy. Granisetron hydrochloride (3 mg on days 1, 8, and 15) and dexamethasone (13.2 mg on day 1 and 6.6 mg on days 2, 3, 8, and 15) were used prior to irinotecan administration in both patients. In addition, aprepitant was administered to both patients for 3-5 days with cisplatin. One of these patients also received aprepitant with irinotecan on days 8 and 15. During chemotherapy, INR was transiently elevated almost 1.5-fold over baseline level on day 3. This variation did not occur in subsequent irinotecan cycles on days 8 and 15. The timing of these increases was similar in each of the cycles. DISCUSSION: Cisplatin was the common drug in the cases presented and therefore could be related to the INR elevations. To our knowledge, these are the first reports of an interaction between warfarin and irinotecan-cisplatin chemotherapy, but reports of a similar interaction with chemotherapy including platinum derivatives exist. Use of the Horn Drug Interaction Probability Scale indicated a probable interaction between warfarin and cisplatin. CONCLUSIONS: Cisplatin might affect the anticoagulation function of warfarin. Careful INR monitoring is necessary during antineoplastic chemotherapy with cisplatin in patients taking warfarin.