A humanized single-chain antibody against beta 3 integrin inhibits pulmonary metastasis by preferentially fragmenting activated platelets in the tumor microenvironment

Zhang, Wei; Dang, Song; Hong, Tao; Tang, Jian; Fan, Jianhui; Bu, Dawei; Sun, Yanjie; Wang, Zhugang; Wısnıewskı, Thomas

doi:10.1182/blood-2012-04-425207

Cited by 49 publications

(44 citation statements)

References 35 publications

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“…Platelets have been suggested to play an important role in cancer progression and metastasis (18). A previous study demonstrated that preliminarily activated platelets have tumor-promoting properties (19). Although the number of studies that have investigated the biological association between MPV and cancer progression is limited, recent clinical reports demonstrated the negative effect of a low MPV on the prognosis of cancer patients.…”

Section: Univariate Analysis Multivariate Analysis ------------------mentioning

confidence: 99%

Prognostic significance of preoperative mean platelet volume in resected non-small-cell lung cancer

Kumagai

Tokuno

Ueda

et al. 2014

Molecular and Clinical Oncology

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Abstract. An increased mean platelet volume (MPV) is an early marker of platelet activation. MPV was also shown to be associated with the pathophysiological characteristics of various types of cancer. A previous study demonstrated that MPV was significantly associated with the overall survival (OS) of patients with advanced non-small-cell lung cancer (NSCLC). However, there has been no analysis of the prognostic effect of MPV on patients with resected NSCLC. The aim of this study was to evaluate the contribution of MPV to the survival of patients with completely resected NSCLC. We retrospectively analyzed 308 consecutive patients with NSCLC who underwent curative resection at Kitano Hospital. The associations between MPV and clinicopathological factors were assessed. We also evaluated the effect of MPV on survival, using the two-tailed log-rank test and the Cox proportional hazards model. A MPV value of 8.50 fl was considered to be the optimal cut-off value for prognosis. A low MPV was not associated with any other clinicopathological factors. The two-tailed log-rank test demonstrated that patients with a low MPV experienced a shorter disease-free survival (DFS) and overall survival (OS) (P=0.011 and 0.001, respectively), compared to those with a high MPV. The multivariate analysis demonstrated that a low MPV was an independent unfavorable prognostic factor for DFS and OS [hazard ratio (HR)=1.713; 95% confidence interval (CI): 1.070-2.742, P=0.025; and HR=2.835; 95% CI: 1.304-6.163, P=0.009, respectively)]. Therefore, we demonstrated that a low MPV predicted an unfavorable prognosis in patients with NSCLC following curative resection.

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Section: Univariate Analysis Multivariate Analysis ------------------mentioning

confidence: 99%

Prognostic significance of preoperative mean platelet volume in resected non-small-cell lung cancer

Kumagai

Tokuno

Ueda

et al. 2014

Molecular and Clinical Oncology

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“…Tumour cells can induce platelet activation through various mechanisms and their metastatic potential correlates with their ability to activate platelets [37][38][39][40] . Pharmacological inhibition of platelet activation 41 , or depletion 5 or inhibition 42 of proteins critical for platelet activation significantly decreased the metastatic potential of tumour cells. To test whether the metastasis-enhancing effect of platelet was dependent on TLR4, WT and TLR4 À / À mice were treated with two mechanistically different antiplatelet agents.…”

Section: Experimental Metastasis Is Diminished In Tlr4-deficient Micementioning

confidence: 99%

Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein

et al. 2014

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Increasing evidence suggests that TLR4 expression by tumour cells promotes tumour progression, but it is unclear whether TLR4 is involved in metastasis. Here we show that TLR4 deficiency significantly diminishes experimental lung metastasis without affecting primary tumour growth. Bone marrow transplantation experiment and application of antiplatelet agents in mice demonstrate that TLR4 on platelets plays an important role in metastasis. TLR4 is critical for platelet-tumour cell interaction in vitro. Furthermore, high-mobility group box1 (HMGB1) neutralization attenuates platelet-tumour cell interaction in vitro and metastasis in vivo in a TLR4-dependent manner, indicating that tumour cell-released HMGB1 is the key factor that interacts with TLR4 on platelets and mediates platelet-tumour cell interaction, which promotes metastasis. These findings demonstrate a mechanism by which platelets promote tumour cell metastasis and suggest TLR4, and its endogenous ligand HMGB1 as targets for antimetastatic therapies.

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“…The relationship between increased lymphocyte ratio on the tissue level and good prognosis has Thrombocytosis occurs after megakaryocytes stimulated by pro-inflammatory cytokines such as IL-1 and IL-6 and is considered an indicator of inflammation severity (15). Activated platelets release angiogenic growth factors and contribute to tumor angiogenesis and progression (16). Based on this idea, platelets are thought to play a significant role in cancer growth and metastasis (17), as a result of which MPV is considered a parameter that indicates inflammation (18) and is used for early detection of platelet activation (19).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and Mean Platelet Volume (MPV) In Patients with Colorectal Carcinoma [Izmir Oncology Group(IZOG) Study]

Oflazoğlu¹,

Alacacıoğlu²,

Somali³

et al. 2017

Acta Oncol Tur.

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ÖZET Giriş ve Amaç:Önceden kolorektal kanser(KRK) genel sağkalım ve rekürrense etki edebilecek çeşitli faktörler tanımlanmıştır. Ancak bunların birkaçı prognostic marker olarak kabul edilir. Mevcut çalışmamızda nötrofil/lenfosit oranı(NLO), trombosit/lenfosit oranı(TLO) ve ortalama trombosit hacminin(OTH) KRK li hastalarada bir biobelirteç olarak potansiyelini araştırmayı amaçladık. Yöntem ve Gereçler: Retrospektif olarak tanı anında metastaik olmayan ve en az 12 aylık takip periyodu sonrasında rekürrens gelişen, 2008-2014 yılları arasında tanı almış 336 KRK tanılı hastanın klinik ve demografik verilerini incelendik. NLO, TLO ve OTH değerlerini belirlemek içi ROC eğrisi analizi kullanıldık. Bulgular: Hastalar nüks eden ve etmeyen olarak 2 gruba kategorize edildi. 89 hastada (%26,5) da takip periyodunda nüks gelişti. NLO≤3.39 olan grupta hastalıksız sağklaım 55.5 bulunurken NLO>3.39 olan grupta hastalıksız sağkalım 82.8 ay bulundu(p<0.0001). TLO≤183 olan grupta hastalıksız sağklaım 57.8 ay bulunurken TLO>183 olan grupta ise hastalıksız sağkalım 78.7 ay bulundu (p: 0.016). OTH≤8.3 olan grupta hastalıksız sağkalım 59.7 ay bulunurken OTH>8.3 olan grupta ise hastalıksız sağklaım 59.7 ay oarak bulundu (p: 0.057) Tartışma ve Sonuç: Bizim çalışmamız NLO, TLO ve OTH seviyelerinin KRK tanılı hastalarda güvenilebilecek prognostic biyobelirteçler olabileceğini göstermiştir. Yeni tanı almış KRK Tanılı hastalardaki NLO, TLO ve OTH değerlerinin artan sitokin seviyesini ve buna bağlı olarak değişimleri yansıması olabilir. Anahtar Kelimeler: kolorektal kanser, ortalama trombosit hacmi, trombosit/lenfosit oranı, nötrofil/lenfosit oranı, biyobelirteç ABSTRACT Introduction: There are various factors that have been determined to affect recurrence and survival in colorectal cancer (CRC). However, few of them exhibit so high a prognostic marker. The present study aimed to investigate the potential of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and mean platelet volume (MPV) as prognostic markers in patients with CRC. Methods: We retrospectively examined the demographic and clinical data of 336 patients with colorectal adenocarcinoma in 2008-2014, which recurred after a 12-month follow-up period; the patients had nonmetastatic cancer at the time of diagnosis. In order to find out NLR, PLR, and MPV cut-off values, ROC curve analysis was used. Results: Patients were categorized into two groups according to positive relapse and negative relapse. 89 patients (26.5%) experienced a relapse in the follow-up period. The group NLR≤3.39 had 55.5 months of disease-free survival (p<0.0001) while the group NLR>3.39 had 82.8 months (p<0.0001). The group PLR≤183 had 57.8 months, the group PLR>183 had 78.7 months (p=0.016); the group MPV≤8.3 had 59.7 months, the group MPV>8.3 had 87.2 months; the group MPV>8.3 had 87.2 months and the group MPV<8.3 had 59.7 months (p=0.057).

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A humanized single-chain antibody against beta 3 integrin inhibits pulmonary metastasis by preferentially fragmenting activated platelets in the tumor microenvironment

Cited by 49 publications

References 35 publications

Prognostic significance of preoperative mean platelet volume in resected non-small-cell lung cancer

Prognostic significance of preoperative mean platelet volume in resected non-small-cell lung cancer

Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein

Prognostic Value of Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and Mean Platelet Volume (MPV) In Patients with Colorectal Carcinoma [Izmir Oncology Group(IZOG) Study]

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