• Growth
• Immune cells
• Metastasis
• Ovarian cancer
• Stromal cells
• Tumor microenvironment

• Humans
• Tumor Microenvironment
• Female
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/therapy
• Neoplasm Metastasis
• Animals

• 2023-MSLH-161 Liaoning Province Joint Fund Project General Funding Scheme Project
• 82103056 National Natural Science Foundation of China, Youth Science Foundation Project
• 2022JH2/101300045 Liaoning Provincial Department of Science and Technology, Liaoning Provincial Applied Basic Research Project

• Flow cytometry
• Malignant Ascites
• MiMeDB
• Microbiota
• TimsTOF

• Catumaxomab
• Malignant ascites
• Mucinous ascites
• Paracentesis
• Peritoneal carcinomatosis

• Humans
• Ascites/therapy
• Ascites/etiology
• Paracentesis/methods
• Peritoneal Neoplasms/complications
• Peritoneal Neoplasms/therapy
• Peritoneovenous Shunt/methods
• Diuretics/therapeutic use
• Palliative Care/methods
• Antineoplastic Agents/therapeutic use

• Ascites
• Candida albicans
• Caspofungin
• Fungal peritonitis
• Neuroendocrine carcinoma

• Sindbis virus
• immunotherapy
• oncolytic virus
• ovarian cancer

• Humans
• Female
• Oncolytic Viruses
• Sindbis Virus
• Oncolytic Virotherapy/methods
• Neoplasm Recurrence, Local/therapy
• Ovarian Neoplasms/pathology
• Immunotherapy/methods
• Vaccines

• P30 CA016087 NCI NIH HHS
• R44 CA250627 NCI NIH HHS
• S10 OD021747 NIH HHS
• NIH 5R44CA250627 NIH HHS

• CAR-T therapy
• Cancer
• Immunity
• Malignant ascites
• Peritoneal dissemination
• Traditional Chinese medicine

• Humans
• Ascites/etiology
• Ascites/therapy
• Quality of Life
• Neoplasm Recurrence, Local
• Immunotherapy
• Peritoneal Neoplasms
• China
• Carcinoma

• adoptive cell therapy
• cancer vaccine
• immune microenvironment
• immunotherapy
• ovarian cancer
• tumor-associated macrophages
• tumor-infiltrating lymphocytes

• Humans
• Female
• Programmed Cell Death 1 Receptor
• Immunotherapy
• T-Lymphocytes, Cytotoxic
• Lymphocytes, Tumor-Infiltrating
• Ovarian Neoplasms/therapy
• Immunosuppressive Agents/pharmacology
• Tumor Microenvironment

• Fondation pour la Recherche Nuovo-Soldati
• National Medical Research Council

• ascites
• liver metastases
• metastatic pancreatic cancer
• peritoneal carcinomatosis
• systemic inflammation

• Humans
• Retrospective Studies
• Ascites/etiology
• Ascites/pathology
• Quality of Life
• Pancreatic Neoplasms/drug therapy
• Liver Neoplasms/drug therapy

• Immune system
• Lymphatic vessel obstruction
• Malignant ascites
• Treatment options
• Treatment prospects
• VEGF

• Biomarkers
• Cancer antigens
• Cell-free DNA
• Circulating tumor cells
• Liquid biopsy
• Multiplexed assays
• Ovarian cancer
• Secretory proteins

• Gastric cancer
• Macrophage migration inhibitory factor (MIF)
• Malignant ascites
• Peritoneal metastasis
• Vascular endothelial growth factor (VEGF)

• Humans
• Animals
• Mice
• Peritoneal Neoplasms/secondary
• Ascites/pathology
• Stomach Neoplasms/pathology
• Vascular Endothelial Growth Factor A/metabolism
• Cell Line, Tumor
• Adenocarcinoma

• 24234 The Cancer Research Society
• 24381 The Cancer Research Society
• 25320 The Cancer Research Society
• CA200572 DOD Peer Reviewed Cancer Research Program

• FAK
• MAPK
• aminosterol
• malignancy
• squalamine
• tumor-associated angiogenesis
• vascular endothelial growth factor (VEGF)

• P30 CA016042 NCI NIH HHS
• U54 CA143930 NCI NIH HHS
• U54 CA143931 NCI NIH HHS
• NCI U54 CA143930 NCI NIH HHS
• UL1 TR001881 NCATS NIH HHS

• angiogenesis
• clinical trials
• gastric cancer
• gastro-esophageal adenocarcinoma
• precision medicine
• targeted therapy

Cell-free DNA—DNA that has been expelled from cells and can be isolated from blood plasma and other body fluids—is a useful tool in medicine, with applications as a biomarker in diagnosis, prognosis, disease profiling, and treatment selection. In oncology, the ease of access to the tumour genome is a major advantage of cell-free DNA, but while this has led to significant research in blood, other body fluids have not received equal attention. This review article summarises the current research into cell-free DNA in non-blood body fluids, highlighting its values and limitations, and suggesting the direction of future studies. We conclude that cell-free DNA from non-blood body fluids may provide additional information to supplement traditional biopsies, allowing informative and improved patient care across many cancer types.

Cell-free DNA (cfDNA) is a useful molecular biomarker in oncology research and treatment, but while research into its properties in blood has flourished, there remains much to be discovered about cfDNA in other body fluids. The cfDNA from saliva, sputum, cerebrospinal fluid, urine, faeces, pleural effusions, and ascites has unique advantages over blood, and has potential as an alternative ‘liquid biopsy’ template. This review summarises the state of current knowledge and identifies the gaps in our understanding of non-blood liquid biopsies; where their advantages lie, where caution is needed, where they might fit clinically, and where research should focus in order to accelerate clinical implementation. An emphasis is placed on ascites and pleural effusions, being pathological fluids directly associated with cancer. We conclude that non-blood fluids are viable sources of cfDNA in situations where solid tissue biopsies are inaccessible, or only accessible from dated archived specimens. In addition, we show that due to the abundance of cfDNA in non-blood fluids, they can outperform blood in many circumstances. We demonstrate multiple instances in which DNA from various sources can provide additional information, and thus we advocate for analysing non-blood sources as a complement to blood and/or tissue. Further research into these fluids will highlight opportunities to improve patient outcomes across cancer types.

• brillouin microscopy
• mechanical properties
• ovarian cancer
• shear flow

• Humans
• Microfluidics
• Ovarian Neoplasms/diagnostic imaging
• Stress, Mechanical
• Tumor Microenvironment

• R00 CA175292 NCI NIH HHS
• R33 CA204582 NCI NIH HHS
• U01 CA202177 NCI NIH HHS
• UL1 TR002489 NCATS NIH HHS

Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In this review, we focus on the management of oncological emergencies in PB malignancies and the potential complication of associated therapeutic interventions.

Biobliographic review of current evidence on the management of oncological emergencies, their potential complications, as well as synthesis of recommendations was performed. The pathogenesis, frequency, related symptoms as well as appropriate investigations are presented.

The oncologic emergencies in PB patients were summarised in six categories: (1) hematological (including febrile neutropaenia, thrombocytopenia, coagulopathies), (2) gastrointestinal (gastric outlet and biliary obstruction, gastrointestinal bleeding), (3) thromboembolic events, (4) ascites, (5) metabolic disorders and (6) neurologic complications. The pathogenesis, frequency, related symptoms as well as appropriate investigations are also presented.

Patients with PB malignancies are at increased risk of a wide variation of medical emergencies. Clinical knowledge, early recognition and collaboration with the relevant specialties are critical to manage these complications effectively, tailoring overall management around the actual prognosis and individuals’ expectations.

• Cholangiocarcinoma
• Complications
• Emergencies
• Gall bladder cancer
• Management
• Pancreatic cancer

• Apoptosis
• Autophagy
• Ceramide
• Chemoresistance
• Ovarian cancer
• Sphingolipid

• ascites volume
• epithelial ovarian cancer
• primary platinum-resistant
• survival

• adipose tissue
• fat-associated lymphoid cluster (FALC)
• milky spots
• obesity
• omentum
• tumor metastasis

Purpose: Experimental study aimed at evaluating whether pleural neoplastic disease is associated with the degree of pleural fibrosis over time caused by talc pleurodesis. The study describes changes in levels of inflammatory mediators and determines whether the course of time involved in progression of neoplastic pleural disease is the factor that influences safety of talc pleurodesis usage in mice.

Materials and Methods: Animals were randomized into two groups: Cancer group (CG) that received intrapleural injection of Lewis cells or Saline group (SG) that received saline injection. After, the animals were subdivided into Early (pleurodesis 3 days after pleural injection) and Late (pleurodesis 7 days after pleural injection) groups. Half of the animals in each group were euthanized 24 hours after pleurodesis (to obtain the inflammatory data); the remaining animals were killed after 8 days (to obtain the scores of pleural fibrosis).

Results: CGs had lower fibrosis scores than SGs comparing early phases to late phases. Inflammation scores were lower in CGs, particularly in Late group. In SGs the inflammation was intense in 100% of the animals.

In Late CG group pleural adhesions had the lowest scores; we found intense fibrosis only in SGs. VEGF and LDH levels had increased in animals with cancer, particularly in Late group. Systemic distribution of talc occurred only in Late CG.

Conclusions: The time for pleural neoplasia to evolve is inversely proportional to the degree of pleural fibrosis. Earlier pleurodesis yielded the best results related to fibrosis, with less systemic inflammation and is safer in mice.

• lung neoplasia
• metastasis
• pleural effusion
• pleurodesis
• talc

• Biomarkers
• CA125
• Flexible FET, electrochemical
• HE4
• MUC1
• Microfluidic
• Molecular imprinting
• Nanosensors
• Prostasin

Bevacizumab improves symptoms via reducing the peritumoral edema and/or normalizing blood brain barrier, and occasionally via reducing the tumor size. However, the effect against active cystic components has not been documented yet.

Between 2008 and 2018, 139 patients with primary or metastatic brain tumors were treated with bevacizumab (BEV) in our institution. The images and symptoms before and after administration of BEV were examined, and changes in size of cysts were evaluated as follows: CR (complete disappearance), PR (reduction by ≥50%), MR (reduction by ≥25%), SD (size change <25%), PD (increase by ≥25%). The effect of BEV on tumor itself was determined according to Response Assessment in Neuro‐Oncology criteria.

Of the 139 patients, 21 (15.1%) had cystic components. The best responses of cysts to BEV treatment were as follows: CR 6, PR 7, MR 4, SD 4. The group of patients with progressively increasing cysts prior to BEV treatment had significant cyst size reduction compared to stable cyst size groups, at initial imaging after BEV (mean 62.6% vs 22.5%, P = .0055) and at best response timing (mean 76.3% vs 32.8%, P = .0050). Patients with cysts showed significant improvement in symptoms after the treatment with BEV compared to patients without cysts (P = .0033). However, response rate was not different between patients with or without cysts. Overall survival after starting BEV was not different between glioblastoma patients with or without cysts.

Bevacizumab is effective against progressively increasing cysts. Although cysts reduction effect and tumor response and/or overall survival are independent, BEV may be effective in patients who are symptomatic due to cyst enlargement.

• bevacizumab
• cyst
• glioblastoma
• metastatic brain tumor
• primary brain tumor

• bevacizumab
• malignant ascites
• ovarian carcinoma
• palliative care

• angiotensin inhibition
• antifibrotic miRNAs
• ascites
• drug delivery
• ovarian cancer

• Bevacizumab
• Everolimus
• Ovarian cancer
• Targeted therapy

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Bevacizumab/administration & dosage
• Bevacizumab/therapeutic use
• Carcinoma, Ovarian Epithelial
• Disease-Free Survival
• Double-Blind Method
• Everolimus/administration & dosage
• Fallopian Tube Neoplasms/drug therapy
• Female
• Humans
• Middle Aged
• Neoplasm Recurrence, Local/drug therapy
• Neoplasms, Glandular and Epithelial/drug therapy
• Ovarian Neoplasms/drug therapy
• Peritoneal Neoplasms/drug therapy

• U10 CA180868 NCI NIH HHS
• U10 CA027469 NCI NIH HHS
• P30 CA008748 NCI NIH HHS
• U10 CA037517 NCI NIH HHS
• U10 CA180822 NCI NIH HHS

Polyphenols, chemically characterized by a polyhydroxylated phenolic structure, are well known for their widespread pharmacological properties: anti-inflammatory, antibiotic, antiseptic, antitumor, antiallergic, cardioprotective and others. Their distribution in food products is also extensive especially in plant foods such as vegetables, cereals, legumes, fruits, nuts and certain beverages. The latest scientific literature outlines a resilient interconnection between cancer modulation and dietary polyphenols by sphingolipid-mediated mechanisms, usually correlated with a modification of their metabolism. We aim to extensively survey this relationship to show how it could be advantageous in cancer treatment or prevention by nutrients. From this analysis it emerges that a combination of classical chemotherapy with nutrients and especially with polyphenols dietary sources may improve efficacy and decreases negative side effects of the antineoplastic drug. In this multifaceted scenario, sphingolipids play a pivotal role as bioactive molecules, emerging as the mediators of cell proliferation in cancer and modulator of chemotherapeutics.

• ceramide
• chemotherapeutics
• curcumin
• flavonoids
• genistein
• nutraceuticals
• nutrients
• resveratrol
• sphingolipids

• Diet
• Food Analysis
• Humans
• Neoplasms/prevention & control
• Polyphenols/pharmacology

The limitations of current anti-angiogenic therapies necessitate other targets with complimentary mechanisms. Here, we show for the first time that soluble E-cadherin (sE-cad) (an 80-kDa soluble form), which is highly expressed in the malignant ascites of ovarian cancer patients, is a potent inducer of angiogenesis. In addition to ectodomain shedding, we provide further evidence that sE-cad is abundantly released in the form of exosomes. Mechanistically, sE-cad-positive exosomes heterodimerize with VE-cadherin on endothelial cells and transduce a novel sequential activation of β-catenin and NFκB signaling. In vivo and clinical data prove the relevance of sE-cad-positive exosomes for malignant ascites formation and widespread peritoneal dissemination. These data advance our understanding of the molecular regulation of angiogenesis in ovarian cancer and support the therapeutic potential of targeting sE-cad. The exosomal release of sE-cad, which represents a common route for externalization in ovarian cancer, could potentially be biomarkers for diagnosis and prognosis.

A soluble form E-cadherin is highly expressed in ovarian cancer. Here, the authors show that soluble E-cadherin is released by ovarian cancer cells packaged in exosomes and promotes tumor angiogenesis through β-catenin and NFkB signaling activation.

• endocrinopathy
• monoclonal gammopathy
• multiple myeloma (MM)
• organomegaly
• pleural effusion
• polyneuropathy
• skin changes (POEMS) syndrome
• vascular endothelial growth factor (VEGF)

• Antineoplastic Agents, Hormonal/therapeutic use
• Ascites/etiology
• Ascites/metabolism
• Dexamethasone/therapeutic use
• Humans
• Male
• Middle Aged
• Multiple Myeloma/complications
• Multiple Myeloma/drug therapy
• Multiple Myeloma/metabolism
• Vascular Endothelial Growth Factor A/blood
• Vascular Endothelial Growth Factor A/metabolism

• intraperitoneal injection
• metastatic colorectal cancer
• serum ascites albumin gradient
• ziv-aflibercept

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/adverse effects
• Ascites/pathology
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Disease Management
• Female
• Humans
• Injections, Intraperitoneal
• Male
• Middle Aged
• Neoplasm Metastasis
• Odds Ratio
• Receptors, Vascular Endothelial Growth Factor/administration & dosage
• Recombinant Fusion Proteins/administration & dosage
• Recombinant Fusion Proteins/adverse effects
• Retrospective Studies
• Treatment Outcome

Malignant ascites manifests as an end‐stage event during the progression of a number of cancers and lacks a generally accepted standard therapy. Interferon‐β (IFN‐β) has been used to treat several cancer indications; however, little is known about the efficacy of IFN‐β on malignant ascites. In the present study, we report on the development of a novel, engineered form of human and murine IFN‐β, each conjugated with a polyethylene glycol molecule (PEG‐hIFN‐β and PEG‐mIFN‐β, respectively). We provide evidence that these IFN‐β molecules retain anti‐viral potency comparable to unmodified IFN‐β in vitro and manifested improved pharmacokinetics in vivo. Interestingly, PEG‐mIFN‐β significantly inhibited the accumulation of ascites fluid and vascular permeability of the peritoneal membrane in models of ovarian cancer and gastric cancer cell xenograft mice. We further show that PEG‐hIFN‐β directly suppresses VEGF₁₆₅‐induced hyperpermeability in a monolayer of human vascular endothelial cells and that PEG‐mIFN‐β enhanced gene expression for a number of cell adhesion related molecules in mouse vascular endothelial cells. Taken together, these findings unveil a hitherto unrecognized potential of IFN‐β in maintaining vascular integrity, and provide proof‐of‐mechanism for a novel and long‐acting pegylated hIFN‐β for the therapeutic treatment of malignant ascites.

• Anti-tumor activity
• malignant ascites
• pegylated interferon-beta
• peritoneal metastasis
• vascular hyperpermeability

• bevacizumab
• cetuximab
• chinese population
• first-line treatment
• metastatic colorectal cancer
• peritoneal metastasis

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors/administration & dosage
• Angiogenesis Inhibitors/therapeutic use
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Bevacizumab/administration & dosage
• Bevacizumab/therapeutic use
• Cetuximab/administration & dosage
• Cetuximab/therapeutic use
• Colorectal Neoplasms/drug therapy
• Female
• Humans
• Male
• Middle Aged
• Registries
• Treatment Outcome
• Young Adult

• R01 AA020103 NIAAA NIH HHS

Key features of advanced ovarian cancer include metastasis via cell clusters in the abdominal cavity and increased chemoresistance. Resveratrol and derivatives of resveratrol have been shown to have antitumour properties. The purpose of this study was to investigate the effect of resveratrol and acetyl-resveratrol on 3D cell aggregates of ovarian cancer, and establish if NF-κB signalling may be a potential target.

Poly-HEMA coated wells were used to produce 3D aggregates of two ovarian cancer cell lines, SKOV-3 and OVCAR-5. The aggregates were exposed to 10, 20 or 30 μM resveratrol or acetyl-resveratrol for 2, 4 or 6 days. Cell growth and metabolism were measured then ELISA, western blot and immunofluorescence were utilised to evaluate VEGF, IL-8 and NF-κB levels.

Resveratrol and acetyl-resveratrol reduced cell growth and metabolism of SKOV-3 aggregates in a dose- and time-dependent manner. After 6 days all three doses of both compounds inhibited cell growth. This growth inhibition correlated with the attenuated secretion of VEGF and a decrease of NF-κB protein levels. Conversely, the secretion of IL-8 increased with treatment. The effects of the compounds were limited in OVCAR-5 cell clusters.

The results suggest that resveratrol and its derivative acetyl-resveratrol may inhibit in vitro 3D cell growth of certain subtypes of ovarian cancer, and growth restriction may be associated with the secretion of VEGF under the control of the NF-κB protein.

• Acetyl-resveratrol
• Cell clusters
• IL-8
• NF-κB
• Ovarian cancer
• Resveratrol
• VEGF

• VEGF
• ascites
• cancer biology
• cancer stem cells
• epithelial-mesenchymal transition (EMT)
• malignant pleural effusion
• tumor therapy

• anatomy
• peritoneum
• vascular anatomy
• vessel

• CA125
• ascites
• chemorefractoriness
• epithelial ovarian cancer
• fibroblast growth factor

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can increase survival of colorectal cancer (CRC) patients with peritoneal metastases (PM). This treatment is associated with high morbidity and mortality rates. Therefore, improvement of patient selection is necessary. Assuming that the clinical phenotype is dictated by biological mechanisms, biomarkers could play a crucial role in this process. Since it is unknown whether and to what extent angiogenesis influences the course of disease in patients with PM, we investigated the expression of two angiogenesis-related markers and their relation to overall survival (OS) in CRC patients after CRS and HIPEC. Clinicopathological data and tissue samples were collected from 65 CRC patients with isolated metastases to the peritoneum that underwent CRS and HIPEC. Whole tissue specimens from PM were evaluated for versican (VCAN) expression, VEGF expression and microvessel density (MVD) by immunohistochemistry. The relation between these markers and OS was assessed using univariate and multivariate analysis. Associations between VEGF expression, VCAN expression, MVD and clinicopathological data were tested. High stromal VCAN expression was associated with high MVD (p = 0.001), better resection outcome (p = 0.003) and high T-stage (p = 0.027). High epithelial VCAN expression was associated with MVD (p = 0.007) and a more complete resection (p < 0.001). In multivariate analysis, simplified peritoneal cancer index (p = 0.001), VEGF expression levels (p = 0.012), age (p = 0.030), epithelial VCAN expression levels (p = 0.042) and lymph node status (p = 0.053) were associated with OS. Concluding, VCAN and VEGF were associated with survival in CRC patients with PM after CRS and HIPEC. Independent validation in a well-defined patient cohort is required to confirm the putative prognostic role of these candidate biomarkers.

• Angiogenesis
• Biomarkers
• Colorectal cancer
• HIPEC
• Peritoneal metastases
• VEGF
• Versican

• Colorectal cancer
• Palliative systemic therapy
• Peritoneal metastases
• Synchronous
• Targeted therapy

The present report illustrates a case of a 37-year-old Indian male patient diagnosed with adenocarcinoma of the sigmoid colon who underwent an anterior resection with total mesorectal excision surgery. He was administered adjuvant chemotherapy with 10 cycles of a FOLFOX-4 (folinic acid, fluorouracil and oxaliplatin) regimen but developed relapse. He was then put on a FOLFIRI (folinic acid, fluorouracil and irinotecan)-aflibercept (Zaltrap) regimen and received 12 cycles during the next 6 months. During the treatment period, a reduction in ascites along with a decline in serum carcinoembryonic antigen (CEA) level was observed, though the tumor size was unchanged. After completion of 12 cycles, the patient was asymptomatic but showed signs of progression in the form of increased CEA level. The FOLFIRI-aflibercept therapy was discontinued, and the patient was given supportive treatment, but he eventually died after another 6 months. The FOLFIRI-aflibercept treatment provided a progression-free survival of 6 months and an overall survival of 1 year to this patient, which corroborates the findings of the VELOUR trial.

• Colon cancer
• FOLFIRI-aflibercept
• FOLFOX