RESUMO
Epithelial ovarian cancer (EOC) is often diagnosed in advanced stage with peritoneal dissemination. Recent studies indicate that aberrant accumulation of collagen fibers in tumor stroma has a variety of effects on tumor progression. We refer to remodeled fibrous stroma with altered expression of collagen molecules, increased stiffness, and highly oriented collagen fibers as tumor-associated fibrosis (TAF). TAF contributes to EOC cell invasion and metastasis in the intraperitoneal cavity. However, an understanding of molecular events involved is only just beginning to emerge. Further development in this field will lead to new strategies to treat EOC. In this review, we focus on the recent findings on how the TAF contributes to EOC malignancy. Furthermore, we will review the recent initiatives and future therapeutic strategies for targeting TAF in EOC.
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Fibrose , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/metabolismo , Animais , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Epiteliais e Glandulares/etiologia , Metástase NeoplásicaRESUMO
Most epithelial ovarian cancer (EOC) patients are diagnosed with peritoneal dissemination. Cellular interactions are an important aspect of EOC cells when they detach from the primary site of the ovary. However, the mechanism remains underexplored. Our study aimed to reveal the role of chondroitin sulfate proteoglycan 4 (CSPG4) in EOC with a major focus on cell-cell interactions. We examined the expression of CSPG4 in clinical samples and cell lines of EOC. The proliferation, migration, and invasion abilities of the CSPG4 knockdown cells were assessed. We also assessed the role of CSPG4 in spheroid formation and peritoneal metastasis in an in vivo model using sh-CSPG4 EOC cell lines. Of the clinical samples, 23 (44.2%) samples expressed CSPG4. CSPG4 was associated with a worse prognosis in patients with advanced EOC. Among the EOC cell lines, aggressive cell lines, including ES2, expressed CSPG4. When CSPG4 was knocked down using siRNA or shRNA, the cell proliferation, migration, and invasion abilities were significantly decreased compared to the control cells. Proteomic analyses showed changes in the expression of proteins related to the cell movement pathways. Spheroid formation was significantly inhibited when CSPG4 was inhibited. The number of nodules and the tumor burden of the omentum were significantly decreased in the sh-CSPG4 mouse models. In the peritoneal wash fluid from mice injected with sh-CSPG4 EOC cells, significantly fewer spheroids were present. Reduced CSPG4 expression was observed in lymphoid enhancer-binding factor 1-inhibited cells. CSPG4 is associated with aggressive features of EOC and poor prognosis. CSPG4 could be a new treatment target for blocking peritoneal metastasis by inhibiting spheroid formation.
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Antígenos , Proteoglicanas de Sulfatos de Condroitina , Neoplasias Ovarianas , Neoplasias Peritoneais , Proteoglicanas , Animais , Feminino , Humanos , Camundongos , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Proteômica , RNA Interferente Pequeno/genéticaRESUMO
OBJECTIVE: Complete-staging surgery is recommended for stage IA ovarian cancer, but may be omitted for various reasons, including the preservation of fertility and an advanced age. We herein investigated the prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer. METHODS: We retrospectively collected data on 4730 patients with malignant ovarian tumors from the databases of multiple institutions and ultimately included 293 with stage IA epithelial ovarian cancer. Limited-staging surgery was defined as one that did not involve hysterectomy, systematic retroperitoneal lymphadenectomy or the collection of ascites cytology. We used an inverse probability of treatment weighting analysis with propensity scores and estimated the hazard ratios of recurrence and death with limited-staging surgery. RESULTS: In total, 176 out of 293 patients (39.9%) were assigned to the limited-staging surgery group. After propensity score adjustments, no significant differences were observed in recurrence-free survival or overall survival between the limited- and complete-staging surgery groups. Even in the subgroup analysis with age stratification, recurrence-free survival and overall survival were similar in the limited- and complete-staging surgery groups. CONCLUSIONS: The present results indicate the limited prognostic impact of limited-staging surgery for stage IA epithelial ovarian cancer.
Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/patologia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologiaRESUMO
OBJECTIVE: The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer. METHODS: We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were treated as derivation set and the other 104 patients as validation set. Using preoperative computed tomography images, we measured the horizontal cross-sectional area at the third lumbar spine level: the (i) psoas major, (ii) iliac and (iii) paraspinal muscle. The clinical information including recurrence-free survival and overall survival were retrospectively collected. These results were validated with external data sets of three hospitals. RESULTS: The median values of the sarcopenia index (cm2/m2) ± standard deviation with the first data of 90 patients using the psoas, iliac and paraspinal muscle were 3.4 ± 1.0, 1.7 ± 0.6 and 12.6 ± 3.2, respectively. In univariate analyses, the sarcopenia indexes measured using the psoas or paraspinal muscle were associated with recurrence-free survival and overall survival. On the other hand, in multivariate analyses, only the sarcopenia index using paraspinal muscle was significantly related to recurrence-free survival (hazard ratio = 3.78, 95% confidence intervals = 1.29-5.97, P = 0.009) and overall survival (hazard ratio = 3.13, 95% confidence interval = 1.18-8.26, P = 0.022). Paraspinal sarcopenia index was also related to overall survival (hazard ratio = 3.74, 95% confidence interval = 1.31-10.72, P = 0.014) even in patients with advanced stage. Serum albumin was significantly correlated with the sarcopenia index (P = 0.012). Within the analysis of the validation set, sarcopenia index using paraspinal muscle was related to recurrence-free survival (hazard ratio = 2.06, P = 0.045) in multivariate analysis and recurrence-free survival (P = 0.009) in patients with advanced stage. CONCLUSIONS: The sarcopenia index using the paraspinal muscle, not psoas, could be a suitable index to predict recurrence-free survival and overall survival in patients with type-II endometrial cancer even in advanced stage.
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Neoplasias do Endométrio , Sarcopenia , Humanos , Feminino , Sarcopenia/diagnóstico por imagem , Sarcopenia/complicações , Estudos Retrospectivos , Músculos Paraespinais , Prognóstico , Neoplasias do Endométrio/complicaçõesRESUMO
Ovarian cancer is an intractable disease that is mostly diagnosed at an advanced stage and has a high recurrence rate. The early development of characteristic peritoneal dissemination via ascites contributes to a poor prognosis. Based on the "seed and soil" theory, ovarian cancer is considered to form a disseminated tumor that interacts with the peritoneum; superficial mesothelial cells are structurally important. Thus far, we have reported that peritoneal mesothelial cells, which originally are ecological defenses, transform into ovarian cancer-associated mesothelial cells, which are allies of cancer. They are found to be actively involved in the formation of a friendly "soil" that promotes the survival of "seeds" of ovarian cancer cells. We also demonstrated that the progression of ovarian cancer and the induction of its refractory nature are partially mediated through competition and cooperation between ovarian cancer and mesothelial cells. We believe that it is necessary to shift the aim of treatment strategies from solely targeting cancer cells to focusing on the crosstalk between the surrounding environment and ovarian cancer, an approach that ultimately aims to achieve "coexistence" with cancer through disease control.
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Cavidade Abdominal , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Peritônio/patologia , Cavidade Abdominal/patologia , Ascite , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
BACKGROUND: The aim of the present study was to investigate the incidence and hallmarks of long-term survivors of recurrent ovarian carcinoma (LTSROC) in a large-scale retrospective cohort of patients from a multicenter study group. METHODS: We performed a regional multicenter retrospective study between January 1986 and September 2021 using clinical data collected under the central pathological review system. Patients who underwent surgery for primary OC at diagnosis and developed recurrent tumors after the initial treatment were included. We defined LTSROC as patients who survived for 5 years or longer after initial tumor recurrence and examined factors affecting the long-term survival of ROC and outcomes of LTSROC. RESULTS: We collected information on patients with malignant ovarian tumors and finally 657 of them that developed ROC were included in the study population. Sixty-eight (10.4%) patients were LTSROC while 399 (60.7%) were short-term survivors of recurrent ovarian carcinoma. In a multivariate logistic regression analysis, negative ascites cytology [odds ratio (OR) 1.865; 95% CI 1.026-3.393; p = 0.041] and a recurrence-free interval (RFI) of 1 year or longer (OR 2.896; 95% CI 1.546-5.425; p < 0.001) were identified as independent factors associated with LTSROC. Approximately 80% of LTSROC presented with solitary recurrent tumors. Furthermore, more than 50% of LTSROC underwent tumor debulking surgery for the first recurrent tumor with or without chemotherapy. CONCLUSION: RFI of 1 year or longer and negative ascites cytology in the initial surgery were identified as independent predictive factors for LTSROC.
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Ascite , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Feminino , Humanos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , SobreviventesRESUMO
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and has a unique metastatic route using ascites, known as the transcoelomic root. However, studies on ascites and contained cellular components have not yet been sufficiently clarified. In this review, we focus on the significance of accumulating ascites, contained EOC cells in the form of spheroids, and interaction with non-malignant host cells. To become resistant against anoikis, EOC cells form spheroids in ascites, where epithelial-to-mesenchymal transition stimulated by transforming growth factor-ß can be a key pathway. As spheroids form, EOC cells are also gaining the ability to attach and invade the peritoneum to induce intraperitoneal metastasis, as well as resistance to conventional chemotherapy. Recently, accumulating evidence suggests that EOC spheroids in ascites are composed of not only cancer cells, but also non-malignant cells existing with higher abundance than EOC cells in ascites, including macrophages, mesothelial cells, and lymphocytes. Moreover, hetero-cellular spheroids are demonstrated to form more aggregated spheroids and have higher adhesion ability for the mesothelial layer. To improve the poor prognosis, we need to elucidate the mechanisms of spheroid formation and interactions with non-malignant cells in ascites that are a unique tumor microenvironment for EOC.
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Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Ascite/patologia , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Ovarianas/patologia , Esferoides Celulares/metabolismo , Microambiente TumoralRESUMO
Adipocyte-rich omentum offers "good soil" for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro coculturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon coculturing with O-ADF. Additionally, exogenous transforming growth factor-ß1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/ß-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks.
Assuntos
Adipócitos/patologia , Fibroblastos Associados a Câncer/patologia , Omento/patologia , Neoplasias Ovarianas/patologia , Microambiente Tumoral , Células 3T3-L1 , Actinas/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Ascite/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Desdiferenciação Celular/efeitos dos fármacos , Movimento Celular , Proliferação de Células , Feminino , Humanos , Imidas/farmacologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Omento/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/secundário , Quinolinas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Proteína Wnt3A/metabolismoRESUMO
BACKGROUND: Epithelial ovarian cancer remains one of the leading causes of cancer deaths among women worldwide, and advanced epithelial ovarian cancer frequently metastasizes to the omentum. The characteristics of metastatic cancer may differ from those of primary ovarian cancer and reflect the unique omental microenvironment. This study investigated metabolomic differences in epithelial ovarian cancers. METHODS: Patients with advanced epithelial ovarian cancer were eligible for this study. Five patients underwent surgery and resection of paired primary ovarian and omental metastatic cancer at Nagoya University. Metabolome analysis was performed in these paired cancer and metastatic cancer tissues through a facility service (C-SCOPE) at Human Metabolome Technologies, Inc. The concentrations of 116 compounds were measured by CE-TOFMS and CE-QqQMS, and 30 metabolic parameters were calculated. For statistical analyses, Welch's t-test was used for comparisons between two independent groups. RESULTS: Metabolite profiles were all different, which reflects diversity among these cancer tissues. Of the measured compounds, urea was the only metabolite that was significantly decreased in omental metastatic cancers compared with the primary cancers (p = 0.031). Moreover, in omental metastatic cancers, the pentose phosphate pathway was more dominant than glycolysis. Furthermore, in some cases, lactic acids in omental metastatic cancers were markedly decreased compared with primary cancers. With regard to histological subtype, the total levels of amino acids, especially the percentage of glutamine, were significantly enriched in serous carcinomas compared with nonserous carcinomas (p = 0.004 and p = 0.001). Moreover, the reduced forms of glutathione and polyamines were also more abundant in serous carcinomas than in nonserous carcinomas (p = 0.025 and 0.048). CONCLUSIONS: The metabolite profiles differed depending on tumor location and histological subtype. Metabolome analysis may be a useful tool for identifying cancer diagnostic and prognostic markers.
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BACKGROUND: We investigated the prognostic impact of complete-staging lymphadenectomy on patients with clinically apparent Stage I endometrioid epithelial ovarian carcinoma. METHODS: We conducted a regional multi-institutional retrospective study between 1986 and 2018. Amongst 4897 patients with malignant ovarian tumours diagnosed under central pathological review, 259 women with Stage I endometrioid epithelial ovarian carcinoma were eligible. We evaluated differences in survival of patients with both pelvic and para-aortic lymphadenectomy (Group A) and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation (Group B). To analyse the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. RESULTS: In total, 145 patients (56.0%) received both pelvic and para-aortic lymphadenectomy. With propensity score-based adjustment, estimated survival was better in Group A compared with that in Group B but not significant. Pelvic and para-aortic lymphadenectomy also led to no significant improvement of overall survival in most of the subgroups. However, point estimations of the hazard ratio for lymphadenectomy in patients with an age of 45 or younger (hazard ratio, 0.304; 95% confidence interval, 0.094-0.982), a Grade 1-2 (hazard ratio, 0.441; 95% confidence interval, 0.204-0.954) and T1c2-3 tumour (hazard ratio, 0.449; 95% confidence interval, 0.164-1.231) were better compared with those with the opposite characteristics. CONCLUSIONS: Complete-staging lymphadenectomy was not a significant prognostic factor in patients with Stage I endometrioid epithelial ovarian carcinoma, where we still need to explore appropriate candidate for the procedure.
Assuntos
Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Excisão de Linfonodo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Pontuação de Propensão , Intervalos de Confiança , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
A 30-year-old nulliparous woman was transferred under suspicion of acute appendicitis, due to the sudden onset of severe right lower quadrant pain at 31 weeks and 4 days of gestation. Magnetic resonance imaging showed a cystic mass measuring 40 mm in diameter in the right lower abdomen. Because the right ovary without edematous swelling was noted adjacent to the cystic mass, isolated tubal torsion was strongly suspected. Emergency gasless laparoendoscopic single-site surgery showed isolated torsion of the right fallopian tube with a paratubal cyst. The right ovary was not involved in this torsion. Because the color tone of the distal portion of the fallopian tube did not recover sufficiently after detorsion, right salpingectomy was performed. Postoperatively, the infusion of magnesium sulfate was initiated due to increased uterine contraction and continued until 36 weeks of gestation. At 38 weeks and 1 day of gestation, uneventful vaginal delivery yielded a healthy female infant.
Assuntos
Doenças das Tubas Uterinas , Laparoscopia , Cisto Parovariano , Adulto , Doenças das Tubas Uterinas/cirurgia , Tubas Uterinas , Feminino , Humanos , Imageamento por Ressonância Magnética , Cisto Parovariano/cirurgia , Gravidez , Salpingectomia , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/cirurgiaRESUMO
Ovarian cancer (OvCa) is one of the leading causes of death due to its high metastasis rate to the peritoneum. Recurrent peritoneal tumors also develop despite the use of conventional platinum-based chemotherapies. Therefore, it is still important to explore the factors associated with peritoneal metastasis, as these predict the prognosis of patients with OvCa. In this study, we investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa). High MITF expression was significantly associated with a poor prognosis in OvCa. Notably, MITF contributed to the motility and invasion of OvCa cells, and specifically with their peri-mesothelial migration. In addition, MITF-positive cells expressed the melanoma cell adhesion molecule (MCAM/CD146), which was initially identified as a marker of melanoma progression and metastasis, and MCAM expression was regulated by MITF. MCAM was also identified as a significant prognostic factor for poor progression-free survival in patients with OvCa. Collectively, our results suggest that MITF is a novel therapeutic target that potentially promotes peritoneal metastasis of OvCa.
Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição Associado à Microftalmia/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Apoptose , Biomarcadores Tumorais/genética , Antígeno CD146/genética , Antígeno CD146/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Humanos , Fator de Transcrição Associado à Microftalmia/genética , Invasividade Neoplásica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Prognóstico , Células Tumorais CultivadasRESUMO
OBJECTIVE: Ovarian carcinoma (OvCa) is more common in the elderly, but also affects the adolescent and young adult (AYA) generation, which refers to those aged 15-39 years. Although the characteristics of OvCa may differ between AYAs and non-AYAs, limited information is currently available on differences in prognostic factors. Therefore, we herein investigated prognostic factors for and the prognosis of OvCa in AYAs. We also examined the prognostic impact of fertility-sparing surgery in a subgroup analysis. METHODS: We retrospectively collected data on 4897 patients with OvCa from the databases of multiple institutions and ultimately included 1161 patients with epithelial ovarian cancer (EOC). We performed a survival analysis to compare AYAs and non-AYAs with backgrounds that conformed to those of AYAs using the propensity score (PS) matching method. A Cox regression analysis was also conducted to evaluate each predictor of recurrence-free survival (RFS) and overall survival (OS) in the original population. As a subgroup analysis, a multivariate analysis stratified by the AYA and non-AYA generations was performed. RESULTS: In total, 119 AYA patients were included in this study. After PS adjustments, no significant differences were observed in RFS or OS between AYAs and non-AYAs. Prognostic factors differed between AYAs and non-AYAs, particularly in histology and cytology. A multivariate analysis stratified by the AYA and non-AYA generations described that uterine-preserving surgery (UPS) did not have a significant impact on the prognosis of AYAs or non-AYAs. In cases with recurrence, no significant differences were observed in RFS and recurrent sites in the two groups. CONCLUSION: Characteristic prognostic factors for EOC in AYAs were identified. The present results indicate the limited prognostic impact of UPS for EOC in AYAs.
Assuntos
Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Pontuação de Propensão , Humanos , Feminino , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Adulto , Estudos Retrospectivos , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Adulto Jovem , Prognóstico , Adolescente , Preservação da Fertilidade/métodos , Fatores Etários , Análise de Sobrevida , Intervalo Livre de DoençaRESUMO
Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25-50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.
Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Pontos de Checagem do Ciclo Celular , Quinases Ciclina-Dependentes/metabolismo , Células HeLa , Apoptose , Proteínas Oncogênicas/metabolismo , Papillomavirus Humano 16/metabolismo , Proliferação de Células , Proteínas Oncogênicas Virais/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
INTRODUCTION: Patients who have experienced vertical rectus abdominis muscle (VRAM) flap reconstruction are under risk of the abdominal incisional hernia (donor site hernia), and laparotomy increases the risk. PRESENTATION OF THE CASE: We present the case of a 71-year-old nulliparous woman who experienced radical vulvectomy against extramammary Paget disease and reconstructive surgery with VRAM flap 7 years ago and developed right ovarian tumor. In this case, right ovarian tumor was removed with laparoscopic surgery, instead of laparotomy, and the risk of incisional hernia was successfully minimized. DISCUSSION: Incisional (donor site) hernia after reconstructive surgery using VRAM flap has been reported in between 2 and 10%. While VRAM flap can fill larger amount of skin and subcutaneous tissue to recipient site, the risk of postoperative incisional hernia of abdominal wall is substantial. CONCLUSION: Reconstructive surgery of with VRAM flap is required for extramammary vulvar Paget disease expanding wide range, and develops the risk of incisional hernia. Laparoscopic surgery should be applied in patients who have experienced VRAM flap reconstruction and developed pelvic tumor for avoiding the risk of incisional hernia as long as it can be allowed on oncologic aspects such as recurrence.
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OBJECTIVE: The clinical significance of a higher BMI on the prognosis of ovarian cancer remains controversial; therefore, a more detailed analysis is demanded. This study investigated the impact of BMI on peritoneum-specific recurrence to clarify the involvement of adipose tissue in the proliferation of cancer cells at sites of peritoneal dissemination. METHODS: Among 4,730 patients with malignant ovarian tumors, 280 diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIC epithelial ovarian cancer and who underwent complete resection in the primary surgery were included in the present study. RESULTS: There were 42, 201, and 37 women in the low, normal, and high BMI groups, respectively. Peritoneum-specific recurrence-free survival and overall survival were both significantly shorter in patients with a high BMI than in those with a normal BMI (p = 0.028 and 0.018, respectively). No significant differences were observed in the distribution of sites of recurrence between these two groups. A multivariate analysis identified obesity as an independent prognostic factor in addition to pT3 tumor staging and positive ascites cytology. CONCLUSIONS: Patients with a high BMI had a significantly worse prognosis than those with a normal BMI, and peritoneal adipose tissue may have contributed to this difference.
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Neoplasias Ovarianas , Peritônio , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Obesidade/complicações , Obesidade/patologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Peritônio/patologia , Prognóstico , Estudos RetrospectivosRESUMO
Ovarian cancer (OvCa), a lethal gynecological malignancy, disseminates to the peritoneum. Mesothelial cells (MCs) act as barriers in the abdominal cavity, preventing the adhesion of cancer cells. However, in patients with OvCa, they are transformed into cancer-associated mesothelial cells (CAMs) via mesenchymal transition and form a favorable microenvironment for tumors to promote metastasis. However, attempts for restoring CAMs to their original state have been limited. Here, we investigated whether inhibition of mesenchymal transition and restoration of MCs by vitamin D suppressed the OvCa dissemination in vitro and in vivo. The effect of vitamin D on the mutual association of MCs and OvCa cells was evaluated using in vitro coculture models and in vivo using a xenograft model. Vitamin D restored the CAMs, and thrombospondin-1 (component of the extracellular matrix that is clinically associated with poor prognosis and is highly expressed in peritoneally metastasized OvCa) was found to promote OvCa cell adhesion and proliferation. Mechanistically, TGF-ß1 secreted from OvCa cells enhanced thrombospondin-1 expression in CAMs via Smad-dependent TGF-ß signaling. Vitamin D inhibited mesenchymal transition in MCs and suppressed thrombospondin-1 expression via vitamin D receptor/Smad3 competition, contributing to the marked reduction in peritoneal dissemination in vivo. Importantly, vitamin D restored CAMs from a stabilized mesenchymal state to the epithelial state and normalized thrombospondin-1 expression in preclinical models that mimic cancerous peritonitis in vivo. MCs are key players in OvCa dissemination and peritoneal restoration and normalization of thrombospondin-1 expression by vitamin D may be a novel strategy for preventing OvCa dissemination.
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Neoplasias Ovarianas , Fator de Crescimento Transformador beta1 , Linhagem Celular Tumoral , Células Epiteliais , Transição Epitelial-Mesenquimal , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Peritônio/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral , Vitamina D/farmacologiaRESUMO
Most patients with ovarian cancer experience recurrence and develop resistance to platinum-based agents. The diagnosis of platinum resistance based on the platinum-free interval is not always accurate and timely in clinical settings. Herein, we used laser ablation inductively coupled plasma mass spectrometry to visualize the platinum distribution in the ovarian cancer tissues at the time of interval debulking surgery after neoadjuvant chemotherapy in 27patients with advanced high-grade serous ovarian cancer. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum throughout the tumor and adjacent stroma. The type A patients treated post-surgery with platinum-based adjuvant chemotherapy showed significantly shorter periods of recurrence after the last platinum-based chemotherapy session (p = 0.020) and were diagnosed with "platinum-resistant recurrence". Moreover, type A was significantly correlated with worse prognosis (p = 0.031). Post-surgery treatment with non-platinum-based chemotherapy could be effective for the patients classified as type A. Our findings indicate that the platinum resistance can be predicted prior to recurrence, based on the platinum distribution; this could contribute to the selection of more appropriate adjuvant chemotherapy, which may lead to improves prognoses.
Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Platina/uso terapêuticoRESUMO
OBJECTIVE: The aim of the present study was to examine the effects of incomplete surgery and adjuvant chemotherapy on the prognosis of patients with intraoperative rupture of capsulated stage I epithelial ovarian cancer (OvCa). METHODS: A regional retrospective study was conducted between 1986 and 2019. Among 4,730 patients with malignant ovarian tumors, 534 women with International Federation of Gynecology and Obstetrics stage IA and IC1 epithelial OvCa were eligible. Differences in survival outcomes were examined between patients with stage IA and IC1 tumors and the effects of uterine preservation, complete-staging lymphadenectomy, and adjuvant chemotherapy were investigated by an in-depth subgroup analysis. To analyze therapeutic effects, baseline imbalances were adjusted using propensity score (PS). RESULTS: The prognosis of patients with stage IC1 tumors was worse than those with stage IA. Surgical spill did not affect the site of recurrence. In the PS-adjusted subgroup analysis, uterine preservation (hazard ratio [HR]=1.669; 95% confidence interval [CI]=1.052-2.744), incomplete-staging lymphadenectomy (HR=1.689; 95% CI=1.211-2.355), and the omission of adjuvant chemotherapy (HR=3.729; 95% CI=2.090-6.653) significantly increased the HR of recurrence for patients with stage IC1 tumors compared to those with stage IA tumors. Adjuvant chemotherapy decreased the impact of rupture with uterine preservation (HR=0.159; 95% CI=0.230-1.168) or incomplete-staging lymphadenectomy (HR=0.987; 95% CI=0.638-1.527). CONCLUSION: The present results suggest intraoperative rupture of capsulated stage I epithelial OvCa is associated with a poor prognosis. When chemotherapy is given for patients receiving incomplete surgery, there is no longer an increased risk of recurrence observed with the rupture.
Assuntos
Recidiva Local de Neoplasia , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND/AIM: Heat shock protein 105 (HSP105) is overexpressed in various cancers, but not in normal tissues. We investigated the expression levels of HSP105 in cervical cancer and the efficacy of immunotherapy targeting HSP105. MATERIALS AND METHODS: Previously, we established human leukocyte antigen-A*02:01 (HLA-A2) restricted HSP105 peptide-specific cytotoxic T lymphocyte (CTL) clones from a colorectal cancer patient vaccinated with an HSP105 peptide. Herein, we evaluated the expression of HSP105 in cervical cancer and cervical intraepithelial neoplasia. Moreover, we tested the effectiveness of an HLA-A2-restricted HSP105 peptide-specific CTL clone against cervical cancer cell lines. RESULTS: HSP105 was expressed in 95% (19/20) of examined cervical cancer tissues. Moreover, the HSP105 peptide-specific CTL clone recognized HSP105- and HLA-A*02:01-positive cervical cancer cell lines and also showed that cytotoxicity against the cervical cancer cell lines depends on HSP105 peptide and HLA class I restricted manners. CONCLUSION: HSP105 could be an effective target for immunotherapy in patients with cervical cancer.