scholarly journals Mechanism of tumour vascularization in experimental lung metastases

2014 ◽  
Vol 235 (3) ◽  
pp. 384-396 ◽  
Author(s):  
Vanessza Szabo ◽  
Edina Bugyik ◽  
Katalin Dezso ◽  
Nora Ecker ◽  
Peter Nagy ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Tumour Vascularization

PROGESTERONE AND PROGESTATIONAL COMPOUNDS IN THE TREATMENT OF ADVANCED ENDOMETRIAL CARCINOMA

1965 ◽  
Vol 49 (3) ◽  
pp. 412-426 ◽  
Author(s):  
Per Bergsjö
Keyword(s):  
Endometrial Carcinoma ◽  
Lung Metastases ◽  
Endometrial Adenocarcinoma ◽  
Cervical Adenocarcinoma ◽  
Tumour Tissue ◽  
Pelvic Tumour ◽  
Histological Alterations

ABSTRACT Various doses of progesterone in oil and of two progestational compounds (17α-hydroxy-19-nor-progesterone caproate and 17α-hydroxyprogesterone p-butoxyphenyl propionate) have been given to 15 patients with recurrent and/or metastatic endometrial adenocarcinoma and to one patient with metastatic cervical adenocarcinoma, for periods of up to 27 weeks. Regression of lung metastases was noted in 4 of 13 patients, softening of pelvic tumour in 2 of 4, and histological alterations of tumour tissue in 4 of 5 patients. In the patient with metastases from a cervical adenocarcinoma, the disease progressed during the treatment. The significance of the observations is discussed.

Non-surgical Treatments for Lung Metastases in Patients with soft Tissue Sarcoma: Stereotactic Body Radiation Therapy (SBRT) and Radiofrequency Ablation (RFA)

2020 ◽  
Vol 16 ◽  
Author(s):  
Cecilia Tetta ◽  
Maria Carpenzano ◽  
Areej Tawfiq J Algargoush ◽  
Marwah Algargoosh ◽  
Francesco Londero ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Stereotactic Body Radiation Therapy ◽  
Lung Metastases ◽  
Disease Free Interval ◽  
Stereotactic Body Radiation ◽  
Free Interval ◽  
Disease Free

Background: Radio-frequency ablation (RFA) and Stereotactic Body Radiation Therapy (SBRT) are two emerging therapies for lung metastases. Introduction: We performed a literature review to evaluate outcomes and complications of these procedures in patients with lung metastases from soft tissue sarcoma (STS). Method: After selection, seven studies were included for each treatment encompassing a total of 424 patients: 218 in the SBRT group and 206 in the RFA group. Results: The mean age ranged from 47.9 to 64 years in the SBRT group and from 48 to 62.7 years in the RFA group. The most common histologic subtype was, in both groups, leiomyosarcoma. : In the SBRT group, median overall survival ranged from 25.2 to 69 months and median disease-free interval from 8.4 to 45 months. Two out of seven studies reported G3 and one G3 toxicity, respectively. In RFA patients, overall survival ranged from 15 to 50 months. The most frequent complication was pneumothorax. : Local control showed high percentage for both procedures. Conclusion: SBRT is recommended in patients unsuitable to surgery, in synchronous bilateral pulmonary metastases, in case of deep lesions and in patients receiving high-risk systemic therapies. RFA is indicated in case of a long disease-free interval, in oligometastatic disease, when only the lung is involved, in small size lesions far from large vessels. : Further large randomized studies are necessary to establish whether these treatments may also represent a reliable alternative to surgery.

scholarly journals Breast Cancer Cell Re-Dissemination from Lung Metastases—A Mechanism for Enhancing Metastatic Burden

2021 ◽  
Vol 10 (11) ◽  
pp. 2340
Author(s):  
Lucia Borriello ◽  
John Condeelis ◽  
David Entenberg ◽  
Maja H. Oktay
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Metastatic Disease ◽  
Breast Cancer Cells ◽  
Lung Metastases ◽  
Primary Tumors ◽  
Metastatic Burden ◽  
First Time ◽  
Do So

Although metastatic disease is the primary cause of mortality in cancer patients, the mechanisms leading to overwhelming metastatic burden are still incompletely understood. Metastases are the endpoint of a series of multi-step events involving cancer cell intravasation, dissemination to distant organs, and outgrowth to metastatic colonies. Here we show, for the first-time, that breast cancer cells do not solely disseminate to distant organs from primary tumors and metastatic nodules in the lymph nodes, but also do so from lung metastases. Thus, our findings indicate that metastatic dissemination could continue even after the removal of the primary tumor. Provided that the re-disseminated cancer cells initiate growth upon arrival to distant sites, cancer cell re-dissemination from metastatic foci could be one of the crucial mechanisms leading to overt metastases and patient demise. Therefore, the development of new therapeutic strategies to block cancer cell re-dissemination would be crucial to improving survival of patients with metastatic disease.

scholarly journals Clinical significance of RBM3 expression in surgically treated colorectal lung metastases and paired primary tumors

2021 ◽  
Vol 123 (4) ◽  
pp. 1144-1156
Author(s):  
Halla Vidarsdottir ◽  
Christina Siesing ◽  
Björn Nodin ◽  
Per Jönsson ◽  
Jakob Eberhard ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Lung Metastases ◽  
Primary Tumors ◽  
Colorectal Lung Metastases ◽  
Rbm3 Expression

scholarly journals Novel strategy to treat lung metastases: Hybrid therapy involving surgery and radiofrequency ablation

2021 ◽  
Author(s):  
Takaaki Hasegawa ◽  
Hiroaki Kuroda ◽  
Noriaki Sakakura ◽  
Yozo Sato ◽  
Shohei Chatani ◽  
...  
Keyword(s):  
Radiofrequency Ablation ◽  
Lung Metastases ◽  
Hybrid Therapy ◽  
Novel Strategy

scholarly journals Multiple endocrinopathies, hypercalcaemia and pancreatitis following combined immune checkpoint inhibitor use- case report and review of literature

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christine Newman ◽  
Oratile Kgosidalwa ◽  
Osamah A. Hakami ◽  
Carmel Kennedy ◽  
Liam Grogan ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Lung Metastases ◽  
Incidental Finding ◽  
Oral Prednisolone ◽  
Thyroid Stimulating Hormone ◽  
Free T4 ◽  
Cross Sectional ◽  
Remarkable Case ◽  
Acth Deficiency

Abstract Background Immune checkpoint inhibitors (ICIs) are a novel class of oncological agents which are used to treat a number of malignancies. To date seven agents have been approved by the Food and Drug Administration (FDA) to treat both solid and haematological malignancies. Despite their efficacy they have been associated with a number of endocrinopathies. We report a unique case of hypophysitis, thyroiditis, severe hypercalcaemia and pancreatitis following combined ICI therapy. Case presentation A 46-year old Caucasian female with a background history of malignant melanoma and lung metastases presented to the emergency department with lethargy, nausea, palpitations and tremors. She had been started on a combination of nivolumab and ipilimumab 24 weeks earlier. Initial investigations revealed thyrotoxicosis with a thyroid stimulating hormone (TSH) of < 0.01 (0.38–5.33) mIU/L, free T4 of 66.9 (7–16) pmol/.L. TSH receptor and thyroperoxidase antibodies were negative. She was diagnosed with thyroiditis and treated with a beta blocker. Six weeks later she represented with polyuria and polydipsia. A corrected calcium of 3.54 (2.2–2.5) mmol/l and parathyroid hormone (PTH) of 9 (10–65) pg/ml confirmed a diagnosis of non-PTH mediated hypercalcaemia. PTH-related peptide and 1, 25-dihydroxycholecalciferol levels were within the normal range. Cross-sectional imaging and a bone scan out ruled bone metastases but did reveal an incidental finding of acute pancreatitis – both glucose and amylase levels were normal. The patient was treated with intravenous hydration and zoledronic acid. Assessment of the hypothalamic-pituitary-adrenal (HPA) axis uncovered adrenocorticotrophic hormone (ACTH) deficiency with a morning cortisol of 17 nmol/L. A pituitary Magnetic Resonance Image (MRI) was unremarkable. Given her excellent response to ICI therapy she remained on ipilimumab and nivolumab. On follow-up this patient’s thyrotoxicosis had resolved without anti-thyroid mediations – consistent with a diagnosis of thyroiditis secondary to nivolumab use. Calcium levels normalised rapidly and remained normal. ACTH deficiency persisted, and she is maintained on oral prednisolone. Conclusion This is a remarkable case in which ACTH deficiency due to hypophysitis; thyroiditis; hypercalcaemia and pancreatitis developed in the same patient on ipilimumab and nivolumab combination therapy. We postulate that hypercalcaemia in this case was secondary to a combination of hyperthyroidism and secondary adrenal insufficiency.

581 Effects of acoustic immune priming with low-intensity focused ultrasound (LOFU) and trabectedin on a murine model of osteosarcoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A616-A616
Author(s):  
Shannon Keisling
Keyword(s):  
Radiation Therapy ◽  
Heat Shock ◽  
Combination Therapy ◽  
Murine Model ◽  
Heat Shock Response ◽  
Cell Activation ◽  
Pulmonary Metastases ◽  
Lung Metastases ◽  
Therapy Group ◽  
Shock Response

BackgroundOsteosarcoma is the most common primary bone tumor and has a peak incidence in adolescence. The prognosis for recurrent and metastatic disease is poor and over one-third of patients with localized disease at presentation will recur after treatment with metastases. LOFU produces non-lethal, transient mechanical and thermal stress to cause protein misfolding, endoplasmic reticulum stress, and induction of the heat shock response (refs). Trabectedin is directly tumoricidal through inhibiting transcription and DNA repair, modulates the tumor microenvironment by selectively depleting M2 macrophages, and inhibits the transcription factor heat shock factor 1 (HSF1) (refs). We hypothesized that combination therapy would synergistically intensify the unfolded protein response and heat shock response to facilitate antigen presenting cell activation and efficient presentation to cytotoxic T cells. To examine this, experiments are being conducted to investigate the effect of LOFU in combination with trabectedin and/or radiation therapy (RT) in a murine model of osteosarcoma.MethodsPalpable (<5 mm) subcutaneous K7M2 murine osteosarcoma tumors in BALB/c mice were treated with a) LOFU, b) trabectedin (intravenous (IV) or intratumoral (IT)), c) LOFU + trabectedin, and d) radiation. Tumor growth (ANOVA (Kruskal-Wallis) with Dunn’s test for multiple comparisons), pulmonary metastases (Fisher’s exact test) and survival (Kaplan-Meier) were measured and analyzed in GraphPad Prism.ResultsMean tumor volume in the combination therapy group (428 mm3) was less than nontreated controls (887 mm3), LOFU alone (670 mm3), trabectedin alone (1218 mm3, p=0.0386). Radiation therapy resulted in complete ablation of the tumors. None of the combination therapy mice had grossly detectable lung metastases at time of death but metastases were present in the trabectedin only (20%), LOFU only (50%), and control (50%) groups (not statistically significant).ConclusionsCombination therapy with trabectedin and LOFU yielded smaller tumor size and fewer pulmonary metastases compared to individual therapies alone.

scholarly journals Iron-Bound Lipocalin-2 from Tumor-Associated Macrophages Drives Breast Cancer Progression Independent of Ferroportin

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Christina Mertens ◽  
Matthias Schnetz ◽  
Claudia Rehwald ◽  
Stephan Grein ◽  
Eiman Elwakeel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Lipocalin 2 ◽  
Tumor Associated Macrophages

Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.

scholarly journals Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
JiangSheng Zhao ◽  
GuoFeng Chen ◽  
Jingqi Li ◽  
Shiqi Liu ◽  
Quan Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle Progression ◽  
Lung Metastases ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
And Migration ◽  
Healthy Liver

Abstract Background PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. Methods PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. Results PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. Conclusions This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.

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