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Cureus Apr 2024Breast cancer is the most common malignancy diagnosed in women. Invasive lobular breast cancer (ILC) is the second most common histologic subtype after invasive ductal...
Breast cancer is the most common malignancy diagnosed in women. Invasive lobular breast cancer (ILC) is the second most common histologic subtype after invasive ductal carcinoma. Metastatic occult primary breast cancer, although rare, is a well-known clinical entity that usually presents with axillary lymphadenopathy without a detectable breast tumour. A perimenopausal woman in her 50s presented with abdominal pain, fatigue, and weight loss. Imaging showed peritoneal carcinomatosis with ascites, ovarian masses, and a lesion in the ascending colon. Gastric and colon biopsies showed infiltration from lobular breast cancer. Diagnostic workup, including mammography, breast ultrasound, and breast MRI, showed no evidence of breast pathology or axillary lymphadenopathy. First-line treatment with goserelin, letrozole, and palbociclib commenced with clinical improvement and radiological response. This case illustrates the challenges faced by clinicians in the diagnosis and treatment of lobular breast cancer without an identifiable primary lesion or axillary lymphadenopathy.
PubMed: 38689671
DOI: 10.7759/cureus.58586 -
Journal of Cancer Research and Clinical... Apr 2024The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal...
PURPOSE
The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy.
METHODS
This retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression.
RESULTS
The PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than -15% had significantly longer OS.
CONCLUSION
CT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis.
Topics: Humans; Stomach Neoplasms; Peritoneal Neoplasms; Female; Male; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Aged; Prognosis; Adult; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38687350
DOI: 10.1007/s00432-024-05707-4 -
Science Advances Apr 2024Slowing peritoneal spread in high-grade serous ovarian cancer (HGSOC) would improve patient prognosis and quality of life. HGSOC spreads when single cells and spheroids...
Slowing peritoneal spread in high-grade serous ovarian cancer (HGSOC) would improve patient prognosis and quality of life. HGSOC spreads when single cells and spheroids detach, float through the peritoneal fluid and take over new sites, with spheroids thought to be more aggressive than single cells. Using our in vitro model of spheroid collective detachment, we determine that increased substrate stiffness led to the detachment of more spheroids. We identified a mechanism where Piezo1 activity increased MMP-1/MMP-10, decreased collagen I and fibronectin, and increased spheroid detachment. Piezo1 expression was confirmed in omental masses from patients with stage III/IV HGSOC. Using OV90 and CRISPR-modified OV90 in a mouse xenograft model, we determined that while both genotypes efficiently took over the omentum, loss of Piezo1 significantly decreased ascitic volume, tumor spheroids in the ascites, and the number of macroscopic tumors in the mesentery. These results support that slowing collective detachment may benefit patients and identify Piezo1 as a potential therapeutic target.
Topics: Animals; Female; Humans; Mice; Cell Line, Tumor; Cystadenocarcinoma, Serous; Ion Channels; Mechanotransduction, Cellular; Neoplasm Grading; Ovarian Neoplasms; Spheroids, Cellular
PubMed: 38669327
DOI: 10.1126/sciadv.adl4463 -
Journal of Immunology (Baltimore, Md. :... Jun 2024NK cells have been shown to exhibit inflammatory and immunoregulatory functions in a variety of healthy and diseased settings. In the context of chronic viral infection...
NK cells have been shown to exhibit inflammatory and immunoregulatory functions in a variety of healthy and diseased settings. In the context of chronic viral infection and cancer, distinct NK cell populations that inhibit adaptive immune responses have been observed. To understand how these cells arise and further characterize their immunosuppressive role, we examined in vitro conditions that could polarize human NK cells into an inhibitory subset. TGF-β1 has been shown to induce regulatory T cells in vitro and in vivo; we therefore investigated if TGF-β1 could also induce immunosuppressive NK-like cells. First, we found that TGF-β1/IL-15, but not IL-15 alone, induced CD103+CD49a+ NK-like cells from peripheral blood NK cells, which expressed markers previously associated with inhibitory CD56+ innate lymphoid cells, including high expression of GITR and CD101. Moreover, supernatant from ascites collected from patients with ovarian carcinoma also induced CD103+CD49a+ NK-like cells in vitro in a TGF-β-dependent manner. Interestingly, TGF-β1/IL-15-induced CD103+CD56+ NK-like cells suppressed autologous CD4+ T cells in vitro by reducing absolute number, proliferation, and expression of activation marker CD25. Collectively, these findings provide new insight into how NK cells may acquire an inhibitory phenotype in TGF-β1-rich environments.
Topics: Humans; Killer Cells, Natural; Interleukin-15; Transforming Growth Factor beta1; Female; Antigens, CD; Ovarian Neoplasms; Integrin alpha Chains; CD56 Antigen; Cells, Cultured; Lymphocyte Subsets; Lymphocyte Activation
PubMed: 38668728
DOI: 10.4049/jimmunol.2300834 -
Current Oncology (Toronto, Ont.) Apr 2024This review of the palliation of various gastro-intestinal (GI) symptoms encountered in cancer patients is by no means exhaustive. Frequent symptoms such as... (Review)
Review
This review of the palliation of various gastro-intestinal (GI) symptoms encountered in cancer patients is by no means exhaustive. Frequent symptoms such as constipation, nausea and vomiting, bowel obstructions, ascites and bleeds will be discussed, focusing on their assessment and most importantly, how to control the associated symptoms. All of these symptoms and GI complications can significantly impact patients' quality of life (QOL) and should be treated as quickly and aggressively as possible.
Topics: Humans; Palliative Care; Quality of Life; Gastrointestinal Diseases; Neoplasms; Nausea; Vomiting; Constipation
PubMed: 38668077
DOI: 10.3390/curroncol31040174 -
Journal of Human Reproductive Sciences 2024Uncommon presentations of granulomatous salpingitis are pseudoxanthoma salpingitis (PSX) and xanthogranulomatous salpingitis (XGS). The clinical features and image...
Uncommon presentations of granulomatous salpingitis are pseudoxanthoma salpingitis (PSX) and xanthogranulomatous salpingitis (XGS). The clinical features and image modalities can mimic ovarian malignancy. Thus, a proper pre-operative evaluation of this entity is vital to avoid radical treatment. Here, we report a case of a 31-year-old woman with primary infertility diagnosed with pseudoxanthoma salpinx. This patient was a known case of endometriosis and presented with gross ascites.
PubMed: 38665618
DOI: 10.4103/jhrs.jhrs_174_23 -
World Journal of Gastrointestinal... Apr 2024Portal vein thrombosis (PVT), a complication of liver cirrhosis, is a major public health concern. PVT prediction is the most effective method for PVT diagnosis and...
BACKGROUND
Portal vein thrombosis (PVT), a complication of liver cirrhosis, is a major public health concern. PVT prediction is the most effective method for PVT diagnosis and treatment.
AIM
To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis.
METHODS
Patients with cirrhosis hospitalized between January 2016 and December 2021 at the First Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved. Following a 1:1 propensity score matching 572 patients with cirrhosis were screened, and relevant clinical data were collected. PVT risk factors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis. Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables. A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT, and its predictive performance was verified using a receiver operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA). Finally, a network calculator was constructed based on the nomograms.
RESULTS
This study enrolled 286 cirrhosis patients with PVT and 286 without PVT. LASSO analysis revealed 13 variables as strongly associated with PVT occurrence. Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors, including etiology, ascites, gastroesophageal varices, platelet count, D-dimer, portal vein diameter, portal vein velocity, aspartate transaminase to neutrophil ratio index, and platelet-to-lymphocyte ratio. LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables. A nomogram was constructed based on the screened independent risk factors. The nomogram had excellent predictive performance, with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups, respectively. Calibration curves and DCA revealed its good clinical performance. Finally, the optimal cutoff value for the total nomogram score was 0.513. The sensitivity and specificity of the optimal cutoff values were 0.822 and 0.706, respectively.
CONCLUSION
A nomogram for predicting PVT occurrence was successfully developed and validated, and a network calculator was constructed. This can enable clinicians to rapidly and easily identify high PVT risk groups.
PubMed: 38660630
DOI: 10.4251/wjgo.v16.i4.1213 -
Molecular Therapy : the Journal of the... Jun 2024Malignant ascites is a common complication resulting from the peritoneal spread of malignancies, and currently lacks effective treatments. We conducted a phase II trial...
Malignant ascites is a common complication resulting from the peritoneal spread of malignancies, and currently lacks effective treatments. We conducted a phase II trial (NCT04771676) to investigate the efficacy and safety of oncolytic adenovirus H101 and virotherapy-induced immune response in 25 patients with malignant ascites. Oncolytic virotherapy achieved an increased median time to repeat paracentesis of 45 days (95% confidence interval 16.5-73.5 days), compared with the preset control value of 13 days. Therapy was well-tolerated, with pyrexia, fatigue, nausea, and abdominal pain as the most common toxicities. Longitudinal single-cell profiling identified marked oncolysis, early virus replication, and enhanced CD8 T cells-macrophages immune checkpoint crosstalk, especially in responsive patients. H101 also triggered a proliferative burst of CXCR6 and GZMKCD8 T cells with promoted tumor-specific cytotoxicity. Further establishment of oncolytic virus-induced T cell expansion signature (OiTE) implicated the potential benefits for H101-responsive patients from subsequent anti-PD(L)1 therapy. Patients with upregulated immune-signaling pathways in tumor cells and a higher proportion of CLEC10A dendritic cells and GZMKCD8 T cells at baseline showed a superior response to H101 treatment. Our study demonstrates promising clinical responses and tolerability of oncolytic adenovirus in treating malignant ascites and provides insights into the relevant cellular processes following oncolytic virotherapy.
Topics: Humans; Oncolytic Virotherapy; Oncolytic Viruses; Ascites; Female; Male; Middle Aged; Adenoviridae; Aged; Single-Cell Analysis; CD8-Positive T-Lymphocytes; Adult; Treatment Outcome; Longitudinal Studies; Virus Replication
PubMed: 38659226
DOI: 10.1016/j.ymthe.2024.04.029 -
Journal of Nanobiotechnology Apr 2024The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in...
The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone II (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal-organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.
Topics: Metal-Organic Frameworks; Liver Neoplasms; Carcinoma, Hepatocellular; Animals; Mice; Humans; Programmed Cell Death 1 Receptor; Cell Line, Tumor; Immune Checkpoint Inhibitors; Tumor Microenvironment; Mice, Inbred BALB C; Saponins; Lymphocytes, Tumor-Infiltrating
PubMed: 38658950
DOI: 10.1186/s12951-024-02469-6 -
Frontiers in Immunology 2024Malignant ascites indicates ovarian cancer progression and predicts poor clinical outcome. Various ascites components induce an immunosuppressive crosstalk between tumor...
INTRODUCTION
Malignant ascites indicates ovarian cancer progression and predicts poor clinical outcome. Various ascites components induce an immunosuppressive crosstalk between tumor and immune cells, which is poorly understood. In our previous study, imbalanced electrolytes, particularly high sodium content in malignant ascites, have been identified as a main immunosuppressive mechanism that impaired NK and T-cell activity.
METHODS
In the present study, we explored the role of high concentrations of ascites proteins and immunoglobulins on antitumoral NK effector functions. To this end, a coculture system consisting of healthy donor NK cells and ovarian cancer cells was used. The anti-EGFR antibody Cetuximab was added to induce antibody-dependent cellular cytotoxicity (ADCC). NK activity was assessed in the presence of different patient ascites samples and immunoglobulins that were isolated from ascites.
RESULTS
Overall high protein concentration in ascites impaired NK cell degranulation, conjugation to tumor cells, and intracellular calcium signaling. Immunoglobulins isolated from ascites samples competitively interfered with NK ADCC and inhibited the conjugation to target cells. Furthermore, downregulation of regulatory surface markers CD16 and DNAM-1 on NK cells was prevented by ascites-derived immunoglobulins during NK cell activation.
CONCLUSION
Our data show that high protein concentrations in biological fluids are able to suppress antitumoral activity of NK cells independent from the mechanism mediated by imbalanced electrolytes. The competitive interference between immunoglobulins of ascites and specific therapeutic antibodies could diminish the efficacy of antibody-based therapies and should be considered in antibody-based immunotherapies.
Topics: Humans; Killer Cells, Natural; Ascites; Female; Antibody-Dependent Cell Cytotoxicity; Ovarian Neoplasms; Cell Line, Tumor; Immunoglobulins; Receptors, IgG; Cell Degranulation; Antigens, Differentiation, T-Lymphocyte; Cetuximab
PubMed: 38646521
DOI: 10.3389/fimmu.2024.1360615