Role of platelet aggregation in metastatic breast cancer patients

Singla, Tanisha; Singla, Gaurav; Ranga, Sunil; Singla, Swati; Arora, Rashmi

doi:10.4103/ijpm.ijpm_817_19

Cited by 8 publications

(5 citation statements)

References 16 publications

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“…Platelets harboring encapsulated agents have demonstrated systemic clearance similar to donor-derived platelets 28 , 39 . Previous studies report that platelets are activated by tumor cells and adhere to tumor cells, a phenomenon referred to as tumor cell-induced platelet aggregation (TCIPA), which can also increase metastasis 50 . Activated platelets release contents from their granules, and platelets loaded with drugs (such as doxorubicin 51 ) release those drugs in the proximity of tumor site 50 .…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies report that platelets are activated by tumor cells and adhere to tumor cells, a phenomenon referred to as tumor cell-induced platelet aggregation (TCIPA), which can also increase metastasis 50 . Activated platelets release contents from their granules, and platelets loaded with drugs (such as doxorubicin 51 ) release those drugs in the proximity of tumor site 50 . However, cancer patients undergoing chemotherapy can be thrombocytopenic, and cancer patients who receive multiple allogenic drug-loaded platelet transfusions could develop refractoriness to platelets due to HLA alloreactivity and subsequently require transfusions with HLA-matched donor platelets loaded with drugs 52 – 54 .…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Human induced pluripotent stem cell-derived platelets loaded with lapatinib effectively target HER2+ breast cancer metastasis to the brain

Bhan

Ansari

Chen

2021

Sci Rep

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Prognosis of patients with HER2+ breast-to-brain-metastasis (BBM) is dismal even after current standard-of-care treatments, including surgical resection, whole-brain radiation, and systemic chemotherapy. Radiation and systemic chemotherapies can also induce cytotoxicity, leading to significant side effects. Studies indicate that donor-derived platelets can serve as immune-compatible drug carriers that interact with and deliver drugs to cancer cells with fewer side effects, making them a promising therapeutic option with enhanced antitumor activity. Moreover, human induced pluripotent stem cells (hiPSCs) provide a potentially renewable source of clinical-grade transfusable platelets that can be drug-loaded to complement the supply of donor-derived platelets. Here, we describe methods for ex vivo generation of megakaryocytes (MKs) and functional platelets from hiPSCs (hiPSC-platelets) in a scalable fashion. We then loaded hiPSC-platelets with lapatinib and infused them into BBM tumor-bearing NOD/SCID mouse models. Such treatment significantly increased intracellular lapatinib accumulation in BBMs in vivo, potentially via tumor cell-induced activation/aggregation. Lapatinib-loaded hiPSC-platelets exhibited normal morphology and function and released lapatinib pH-dependently. Importantly, lapatinib delivery to BBM cells via hiPSC-platelets inhibited tumor growth and prolonged survival of tumor-bearing mice. Overall, use of lapatinib-loaded hiPSC-platelets effectively reduced adverse effects of free lapatinib and enhanced its therapeutic efficacy, suggesting that they represent a novel means to deliver chemotherapeutic drugs as treatment for BBM.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Human induced pluripotent stem cell-derived platelets loaded with lapatinib effectively target HER2+ breast cancer metastasis to the brain

Bhan

Ansari

Chen

2021

Sci Rep

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“…There were 4 subjects in group I and 12 in group II having ADP <60, 26 subjects in group I and 28 in group II with ADP 61-72 and 10 subjects in group I with ADP >72. Singla et al, [18] studied the role of platelet aggregation in metastatic breast cancer patients using ADP and thrombin among 30 cases (n = 30) of metastatic breast cancer and 30 controls (n = 30) of non metastatic breast cancer which were clinically diagnosed and histopathologically confirmed. In this study, increased aggregation was seen with ADP and thrombin in the metastatic cases and none showed increased aggregation in the non metastatic breast cancer patients.…”

Section: Methodsmentioning

confidence: 99%

Assessment of Role of Platelet Aggregation in Metastatic Breast Cancer Patients

Ramji¹,

Shanmugan²

2022

AIMDR

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Background: To assess role of platelet aggregation in metastatic breast cancer patients.Methods:40 cases (Group I) of metastatic breast cancer patients and equal number of healthy control (Group II) subjects were included. Platelet aggregation studies in vitro using ADP and Thrombin were performed using an optical aggregometer. Detection of platelet aggregation was done by Chrono log series 490 dual and four channel optical aggregometer systems.Results:There were 4 subjects in group I and 12 in group II having ADP <60, 26 subjects in group I and 28 in group II with ADP 61-72 and 10 subjects in group I with ADP >72. Low thrombin <58 was seen in 8 in group II, normal thrombin between 61-72 was seen among 11 in group I and 32 in group II and high thrombin >82 among 29 in group I respectively. Amongst patients with normal platelet count, 14 patients had platelet aggregation with ADP in the normal range and 4 patients had platelet aggregation with ADP in the lower range. In patients with high platelet count, 12 showed aggregation in the normal range, and 10 patients showed aggregation in the higher range which was statistically significant (P< 0.05) (Table III, Graph II).Conclusion: Platelet aggregation has an important part to play in the tumor metastasis of breast cancer patients.

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“…Aspirin is a known inhibitor of platelet aggregation and was recently shown to also attenuate platelet protein release. 24 These previous findings made us exclude the on anti-platelet therapy from our study population but this issue is worth evaluation in future studies.…”

Section: *We Have Multiple Locations Of Lap In Some Of the Patientsmentioning

confidence: 97%

Platelet Activation and Platelet Indices as Markers for Disease Progression in Women with Breast Cancer

Tera

Azzam²,

Abousamra

et al. 2022

Arch Breast Cancer

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Background: Several studies reported the role platelet activation, platelet volume (MPV) and other Indices in breast cancer but the data is inconsistent and/or diverse. The aim of this study was to systematically evaluate the role of platelet activation and platelet volume indices in women with BC as predictors for cancer progression and poor prognosis. Methods: Patients were recruited from our local oncology center between 2019 to 2020 following ethics approval. 80 patients with locally invasive BC, 20 metastatic and 100 controls were recruited. ADP-induced platelet activation was assessed by light-transmission aggregometry. Platelet P-selectin (CD62P) expression with and without ADP stimulation was assessed by flow cytometry. A comprehensive analysis of platelet count and platelet volume indices (PVIs) (MPV, PDW, MPV/P and PDW/P) was conducted. Data were analyzed in relation to tumor pathology, hormone receptors (ER, PR, HER-2) and proliferation index Ki-67. Regression analyses were conducted for the prediction of poor prognosis, tumor aggression and metastatic potential. Results: We found a significant increase in platelet aggregation (MA), CD62P expression, CD62P+ADP, MPV, PDW, MPV/P and PDW/P in the metastatic group compared to the locally invasive group. Univariate regression analysis showed significance for ADP, MA, CD62P+ADP, MPV and PDW/P. Conclusion: MPV/P and PDW/P can be used as simple low-cost predictors for cancer progression and poor prognosis. We conclude platelet activation and specific platelet indices can help predict prognosis in females with BC.

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Role of platelet aggregation in metastatic breast cancer patients

Cited by 8 publications

References 16 publications

RETRACTED ARTICLE: Human induced pluripotent stem cell-derived platelets loaded with lapatinib effectively target HER2+ breast cancer metastasis to the brain

RETRACTED ARTICLE: Human induced pluripotent stem cell-derived platelets loaded with lapatinib effectively target HER2+ breast cancer metastasis to the brain

Assessment of Role of Platelet Aggregation in Metastatic Breast Cancer Patients

Platelet Activation and Platelet Indices as Markers for Disease Progression in Women with Breast Cancer

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