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1.
Cell Death Dis ; 15(4): 247, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575576

RESUMO

The primary site of metastasis for epithelial ovarian cancer (EOC) is the peritoneum, and it occurs through a multistep process that begins with adhesive contacts between cancer cells and mesothelial cells. Despite evidence that Notch signaling has a role in ovarian cancer, it is unclear how exactly it contributes to ovarian cancer omental metastasis, as well as the cellular dynamics and intrinsic pathways that drive this tropism. Here we show that tumor cells produced the Notch ligand Jagged2 is a clinically and functionally critical mediator of ovarian cancer omental metastasis by activating the Notch signaling in single-layered omental mesothelial cells. In turn, Jagged2 promotes tumor growth and therapeutic resistance by stimulating IL-6 release from mesothelial cells. Additionally, Jagged2 is a potent downstream mediator of the omental metastasis cytokine TGF-ß that is released during omental destruction. Importantly, therapeutic inhibition of Jagged2-mediated omental metastasis was significantly improved by directly disrupting the Notch pathway in omental mesothelial cells. These findings highlight the key role of Jagged2 to the functional interplay between the TGF-ß and the Notch signaling pathways during the metastatic process of ovarian cancer cells to the omentum and identify the Notch signaling molecule as a precision therapeutic target for ovarian cancer metastasis.


Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Neoplasias Retroperitoneais , Feminino , Humanos , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Metástase Neoplásica , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
2.
Zhonghua Yi Xue Za Zhi ; 104(16): 1337-1340, 2024 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-38644279

RESUMO

Peritoneal metastasis is the common route of metastasis in gastric cancer and is a major cause of death in advanced gastric cancer. Early intervention with comprehensive treatment can effectively improve the prognosis of some patients with peritoneal metastasis. However, early peritoneal metastasis in gastric cancer is predominantly micro-metastasis, which cannot be effectively evaluated by imaging studies. Moreover, the detection of disseminated cancer cells in peritoneal lavage suffers from a low detection rate and significant heterogeneity. In recent years, the development and application of new liquid biopsy technologies such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have provided new means to assess potential peritoneal metastasis at the cellular and molecular levels, gradually becoming research hotspots in this field. This review will summarize the relevant progress of liquid biopsy in peritoneal metastasis, which holds significant importance for improving the prognosis of gastric cancer patients in China.


Assuntos
DNA Tumoral Circulante , Células Neoplásicas Circulantes , Neoplasias Peritoneais , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Humanos , Biópsia Líquida/métodos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/diagnóstico , Prognóstico
3.
World J Surg Oncol ; 22(1): 99, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38627808

RESUMO

BACKGROUND: Colorectal peritoneal metastases (CRPM) are present in 10-20% of patients at the time of their initial cancer diagnosis, and affects over 20% of those who develop colorectal cancer recurrence. Cytoreductive surgery (CRS) with HIPEC is firmly established as the optimal surgical treatment, but there is very little known about the benefit of repeat or iterative CRS. The aim of this review is to provide a systematic evaluation of the perioperative complications, survival outcomes and quality of life in patients undergoing repeat CRS with HIPEC for CRPM. METHODS: A systematic review of PubMed, Ovid MEDLINE, EMBASE, Scopus and Cochrane databases was performed to identify all studies that reported outcomes for repeat CRS with or without HIPEC for CRPM. RESULTS: Four hundred and ninety-three manuscripts were screened, and 15 retrospective studies were suitable for inclusion. Sample sizes ranged from 2 to 30 participants and comprised a total of 229 patients. HIPEC was used in all studies, but exact rates were not consistently stated. Perioperative morbidity was reported in four studies, between 16.7% and 37.5%. Nine studies reported mortality rate which was consistently 0%. The median overall survival after repeat CRS ranged from 20 to 62.6 months. No studies provided quality of life metrics. CONCLUSION: Repeat CRS for CRPM has perioperative morbidity and mortality rates comparable to initial CRS, and offers a potential survival benefit in selected patients. There is however limited high-quality data in the literature.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/secundário , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução , Estudos Retrospectivos , Qualidade de Vida , Recidiva Local de Neoplasia/patologia , Terapia Combinada , Taxa de Sobrevida , Protocolos de Quimioterapia Combinada Antineoplásica
4.
Clin Exp Med ; 24(1): 80, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642130

RESUMO

Peritoneal mesothelioma (PeM) is an aggressive tumor with limited treatment options. The current study aimed to evaluate the value of next generation sequencing (NGS) of PeM samples in current practice. Foundation Medicine F1CDx NGS was performed on 20 tumor samples. This platform assesses 360 commonly somatically mutated genes in solid tumors and provides a genomic signature. Based on the detected mutations, potentially effective targeted therapies were identified. NGS was successful in 19 cases. Tumor mutational burden (TMB) was low in 10 cases, and 11 cases were microsatellite stable. In the other cases, TMB and microsatellite status could not be determined. BRCA1 associated protein 1 (BAP1) mutations were found in 32% of cases, cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) and neurofibromin 2 (NF2) mutations in 16%, and ataxia-telangiectasia mutated serine/threonine kinase (ATM) in 11%. Based on mutations in the latter two genes, potential targeted therapies are available for approximately a quarter of cases (i.e., protein kinase inhibitors for three NF2 mutated tumors, and polyADP-ribose polymerase inhibitors for two ATM mutated tumors). Extensive NGS analysis of PeM samples resulted in the identification of potentially effective targeted therapies for about one in four patients. Although these therapies are currently not available for patients with PeM, ongoing developments might result in new treatment options in the future.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Mesotelioma/diagnóstico , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Neoplasias Pulmonares/genética , Mutação , Genômica , Biomarcadores Tumorais/genética , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/genética
5.
World J Surg Oncol ; 22(1): 103, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637820

RESUMO

BACKGROUND: Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. METHODS: A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). RESULTS: A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). CONCLUSION: Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/patologia , Procedimentos Cirúrgicos de Citorredução , Neoplasias Colorretais/patologia , Terapia Neoadjuvante , Peritônio/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
6.
BMJ Open ; 14(4): e075680, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38643004

RESUMO

INTRODUCTION: Accurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer and mainly diagnosed by diagnostic laparoscopy and peritoneal lavage evaluation. However, diagnostic laparoscopy is invasive and less cost-effective. It is urgent to develop a safe, fast and non-invasive functional imaging method to verify the peritoneal metastasis of gastric cancer. The aim of our study was to evaluate the proportion of patients in whom 68Ga-FAPI-04 positron emission tomography/CT (PET/CT) led to a change in treatment strategy and to assess the diagnostic accuracy of 68Ga-FAPI-04 PET/CT for the detection of occult peritoneal metastasis compared with laparoscopic exploration. METHODS AND ANALYSIS: In this single-centre, prospective diagnostic test accuracy study, a total of 48 patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma (cT4a-b, N0-3, M0, based on CT images) who are considering radical tumour surgery will be recruited. All participants will undergo 68Ga-FAPI-04 PET/CT before the initiation of laparoscopic exploration. The primary outcome is the proportion of patients with occult peritoneal metastatic lesions detected by 68Ga-FAPI-04 PET/CT, leading to a change in therapy strategy. The secondary outcomes include the diagnostic performance of 68Ga-FAPI-04 PET/CT for occult peritoneal metastasis, including sensitivity, specificity, accuracy, positive predictive value and negative predictive value. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (2022-1484). Study results will be presented at public and scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300067591.


Assuntos
Laparoscopia , Neoplasias Peritoneais , Quinolinas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Radioisótopos de Gálio , Estudos Prospectivos , Neoplasias Peritoneais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Fluordesoxiglucose F18
7.
Cell Mol Life Sci ; 81(1): 189, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38643448

RESUMO

Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-ß1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-ß signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-ß1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-ß signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.


Assuntos
Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/genética , Fator de Crescimento Transformador beta1 , Glicólise , Neoplasias Colorretais/genética , Células-Tronco , Microambiente Tumoral , Proteína Smad3/genética , Proteína 4 Semelhante a Angiopoietina/genética
8.
J Med Case Rep ; 18(1): 200, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644500

RESUMO

INTRODUCTION: Lipomas arising in the parietal peritoneum are rare, and some of them cause abdominal pain due to torsion of the pedunculated peritoneum. We encountered a case of parietal peritoneal lipoma arising upper peritoneum. In this report, we describe the detail of clinical presentation and discuss its potential pathogenesis and treatment strategy. CASE PRESENTATION: 45 year-old Japanese female patient presented with long-lasting intermittent pain in the left upper abdominal region. Abdominal imaging showed a well-defined fatty mass measuring 40 mm in size, suggesting a parietal peritoneal lipoma. Laparoscopy revealed a tumor with a twisted peduncle; however, no adhesion of the surrounding tissues and ischemic changes were visible. The tumor was easily removed by dissection of the tumor pedicle. CONCLUSION: Parietal peritoneal lipoma often shows pedunculated form and it causes abdominal pain by the torsion of tumor pedicle. Therefore, this type of lipoma should be considered a more aggressive surgery.


Assuntos
Dor Abdominal , Laparoscopia , Lipoma , Neoplasias Peritoneais , Humanos , Feminino , Lipoma/cirurgia , Lipoma/complicações , Lipoma/diagnóstico por imagem , Pessoa de Meia-Idade , Dor Abdominal/etiologia , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/complicações , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
Langenbecks Arch Surg ; 409(1): 113, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589714

RESUMO

PURPOSE: Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM. METHODS: A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins. RESULTS: Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69 years. CONCLUSION: Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.


Assuntos
Hipertermia Induzida , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/patologia , Peritônio , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução , Estudos Retrospectivos , Centros de Atenção Terciária , Qualidade de Vida , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Taxa de Sobrevida
11.
Sci Rep ; 14(1): 7832, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570542

RESUMO

The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.


Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Camundongos , Animais , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Camundongos Endogâmicos C57BL , Omento/patologia , Nervo Vago/cirurgia , Nervo Vago/patologia
12.
PLoS One ; 19(4): e0300594, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38574044

RESUMO

BACKGROUND: Peritoneal sarcomatosis (PS) is a difficult entity to treat with limited options and guarded prognosis. We aimed to determine if the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) could offer superior local recurrence-free survival in patients with retroperitoneal sarcoma at high risk of developing PS as opposed to extended resection alone. METHODS: This is a single arm, phase II intervention study where all patients with recurrent localized retroperitoneal sarcoma considered at high risk of developing PS were considered for enrolment (ClinicalTrials.gov identifier: NCT03792867). Upon enrolment, patients underwent vigorous preoperative testing to ensure fitness for the procedure. During surgery, patients underwent extended resection and HIPEC with doxorubicin. Patients were followed-up every 2 weeks (± 10 days) for the first month and subsequently every three months (± 1 month) up to a year post-surgery, and were assessed for potential chemotherapy toxicity and post-treatment complications. After a year from resection and HIPEC, patients were followed-up either during routine clinic review or contacted via telephone every year (± 1 month) for 3 years. RESULTS: Six patients were recruited but one patient dropped out due to adverse and unexpected intraoperative events. The remaining patients completed the procedure uneventfully. Post-HIPEC, all patients recurred with a disease-free interval ranging from six to 24 months. Three patients died due to complications from recurrent disease whereas the remaining three patients are alive as of their last visit. The overall survival at time at reporting ranged between 22 to 56 months. CONCLUSION: The procedure is feasible with no major morbidity to patients. However, we are unable to recommend for it to be implemented as a routine procedure at this current stage due to lack of improved survival outcomes. Further multi-institutional studies may be conducted to yield better results.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Retroperitoneais , Sarcoma , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Projetos Piloto , Terapia Combinada , Hipertermia Induzida/métodos , Neoplasias Peritoneais/cirurgia , Sarcoma/tratamento farmacológico , Sarcoma/cirurgia , Neoplasias Retroperitoneais/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução
14.
Cancer Med ; 13(6): e7101, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38506243

RESUMO

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical malignant syndrome, and its rarity causes a lack of pathology research. This study aims to quantitatively analyze HE-stained pathological images (PIs), and develop a new predictive model integrating digital pathological parameters with clinical information. METHODS: Ninety-two PMP patients with complete clinic-pathological information, were included. QuPath was used for PIs quantitative feature analysis at tissue-, cell-, and nucleus-level. The correlations between overall survival (OS) and general clinicopathological characteristics, and PIs features were analyzed. A nomogram was established based on independent prognostic factors and evaluated. RESULTS: Among the 92 PMP patients, there were 34 (37.0%) females and 58 (63.0%) males, with a median age of 57 (range: 31-76). A total of 449 HE stained images were obtained for QuPath analysis, which extracted 40 pathological parameters at three levels. Kaplan-Meier survival analysis revealed eight clinicopathological characteristics and 20 PIs features significantly associated with OS (p < 0.05). Partial least squares regression was used to screen the multicollinearity features and synthesize four new features. Multivariate survival analysis identified the following five independent prognostic factors: preoperative CA199, completeness of cytoreduction, histopathological type, component one at tissue-level, and tumor nuclei circularity variance. A nomogram was established with internal validation C-index 0.795 and calibration plots indicating improved prediction performance. CONCLUSIONS: The quantitative analysis of HE-stained PIs could extract the new prognostic information on PMP. A nomogram established by five independent prognosticators is the first model integrating digital pathological information with clinical data for improved clinical outcome prediction.


Assuntos
Neoplasias Peritoneais , Pseudomixoma Peritoneal , Masculino , Feminino , Humanos , Pseudomixoma Peritoneal/patologia , Prognóstico , Nomogramas , Análise de Sobrevida , Estudos Retrospectivos
15.
Cell Death Dis ; 15(3): 218, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490994

RESUMO

Gastric cancer (GC), notorious for its poor prognosis, often advances to peritoneal dissemination, a crucial determinant of detrimental outcomes. This study intricately explores the role of the TGFß-Smad-LIF axis within the tumor microenvironment in propagating peritoneal metastasis, with a specific emphasis on its molecular mechanism in instigating Neutrophil Extracellular Traps (NETs) formation and encouraging GC cellular functions. Through a blend of bioinformatics analyses, utilizing TCGA and GEO databases, and meticulous in vivo and in vitro experiments, LIF was identified as pivotally associated with GC metastasis, notably, enhancing the NETs formation through neutrophil stimulation. Mechanistically, TGF-ß was substantiated to elevate LIF expression via the activation of the Smad2/3 complex, culminating in NETs formation and consequently, propelling peritoneal metastasis of GC. This revelation uncovers a novel potential therapeutic target, promising a new avenue in managing GC and mitigating its metastatic propensities.


Assuntos
Armadilhas Extracelulares , Neoplasias Peritoneais , Neoplasias Gástricas , Fator de Crescimento Transformador beta , Humanos , Armadilhas Extracelulares/metabolismo , Neutrófilos/metabolismo , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Neoplasias Gástricas/patologia , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Fator Inibidor de Leucemia/metabolismo , Transdução de Sinais
16.
Curr Oncol ; 31(3): 1445-1459, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38534942

RESUMO

Peritoneal metastasis is a common finding in patients with advanced gastric cancer. Beyond systemic chemotherapy, additive local treatments such as cytoreductive surgery and intraperitoneal chemotherapy are considered an inherent part of different multimodal treatment concepts for selected patients with peritoneal metastatic gastric cancer. This review article discusses the role of cytoreductive surgery (CRS) and intraperitoneal chemotherapy, including HIPEC, NIPS, and PIPAC, as additive therapeutic options with curative and palliative intent.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Peritoneais/secundário , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
17.
Anticancer Res ; 44(4): 1553-1557, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537963

RESUMO

BACKGROUND/AIM: Among postoperative complications, fascial dehiscence (FD) is registered in up to 10% of patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). This study aimed to evaluate the risk factors related to FD after CRS-HIPEC. PATIENTS AND METHODS: A retrospective analysis of a prospectively maintained database of consecutive patients who underwent CRS-HIPEC between 2015 and 2023 was performed. For each patient, risk factors for postoperative fascial dehiscence were identified using multivariate analysis. RESULTS: During the study period (2018-2023), 217 patients were treated with CRS-HIPEC. The incidence of FD was observed in seven cases (3.2%), which were reoperated with direct fascial closure. In three cases, FD was associated with other grade III-IV complications. Body mass index, (BMI; p=0.024), doxorubicin-based HIPEC (p=0.005), and open technique (p=0.004) were identified as risk factors for FD in univariate analysis. Systemic chemotherapy, prior surgical score, and peritoneal cancer index (PCI) were not associated with an increased risk of FD. In multivariable regression analysis, doxorubicin-based HIPEC and open technique were confirmed as risk factors for FD. CONCLUSION: Although FD is a relatively rare event after CRS-HIPEC, open technique and doxorubicin-based HIPEC were significant predictors of this complication. Specific fascial closure techniques and proper wound care should be considered in high-risk patients.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/patologia , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Estudos Retrospectivos , Hipertermia Induzida/efeitos adversos , Doxorrubicina/efeitos adversos , Fatores de Risco , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Taxa de Sobrevida
18.
Methods Cell Biol ; 185: 67-78, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38556452

RESUMO

Peritoneal carcinomatosis (PCa) represents a metastatic stage of a disease with unmet therapeutic options. Malignant cells from primary tumors (gastrointestinal or gynecologic malignancies) invade the peritoneal cavity and eventually seed onto peritoneal surfaces, with the omentum being the most common nest area. With a median survival of less than 6 months, PCa has a dismal prognosis that can be improved with treatments only available to a select few individuals with low tumor burden. Thus, the discovery of novel and effective therapies for this disease depends on reliable animal models. Here, we describe a method to generate syngeneic PCa mouse models based on intraperitoneal (i.p.) administration of tumor cells. This model allows to follow-up cancer progression in PCa models from ovarian and colorectal origins monitoring mice bodyweight changes, ascites development and overall survival. Moreover, luciferase-expressing tumor cells can also be used to assess tumor growth after i.p. injection through in vivo bioluminescence quantification. The establishment of reliable, easy-to-monitor and reproducible intraperitoneal syngeneic tumors models, as described here, is the first step to develop cutting-edge therapies against PCa.


Assuntos
Neoplasias Peritoneais , Camundongos , Feminino , Animais , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Modelos Animais de Doenças
19.
Medicina (Kaunas) ; 60(3)2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38541186

RESUMO

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis.


Assuntos
Carcinoma , Neoplasias Ovarianas , Neoplasias Peritoneais , Teratoma , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Carcinoma/diagnóstico , Carcinoma/cirurgia , Teratoma/diagnóstico , Teratoma/cirurgia , Teratoma/patologia
20.
Anal Chim Acta ; 1301: 342488, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38553118

RESUMO

Gastric cancer (GC) was one of the most common cancers with high mortality. The detection of GC peritoneal metastasis had important significance. In this work, we have developed the novel electrochemiluminescence (ECL) biosensor to detect microRNA in GC extracellular vesicle (EV). Firstly, in situ growth of Cu nanocluster (Cu NC) on the metal-organic frameworks (MOFs) nanosheet was achieved successfully. Due to the confinement effect, Cu NCs in the porous structure of Zn MOF possessed the high quantum yield and good stability. Meanwhile, Zn MOF provided good electrochemical activity for the ECL reaction. Furthermore, the nanosized MOFs did not only act as sensing platform to load Cu NCs and link biomolecules, but also reduce steric hindrance effect for biomolecular recognition. Additionally, Au NPs/MXene and phospholipid layer were prepared and modified on the electrode, which can regulate electron transfer and improve the target recognition efficiency. The Cu NCs/Zn MOF nanosheet-based ECL sensor was employed to detect miRNA-421 from 1 fM to 1 nM with a detection limit of 0.5 fM. Finally, extracellular vesicles form clinic GC patient ascites were extracted and analyzed. The results showed that the constructed biosensor can be used for the GC peritoneal metastasis diagnosis.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , MicroRNAs , Neoplasias Peritoneais , Humanos , Estruturas Metalorgânicas/química , Medições Luminescentes/métodos , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Limite de Detecção , Nanopartículas Metálicas/química
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