Dapatkah D-dimer Digunakan sebagai Penanda Koagulasi pada Kanker?

Pasien kanker mempunyai risiko tinggi untuk mengalami trombosis, terutama tromboemboli vena (TEV).. Pasien kanker yang mengalami TEV mempunyai risiko mortalitas yang lebih tinggi dibandingkan dengan pasien kanker tanpa TEV.Faktor-faktor risiko yang berkaitan dengan terjadinya trombosis pada pasien kanker bersifat multipel dan kompleks, tidak hanya akibat cancer procoagulant yang dilepaskan oleh sel kanker, tetapi juga jenis kanker, stasis akibat masa tumor, respons tubuh dari pejamu (penderita kanker), dan pengobatan yang dijalani oleh pasien tersebut. Pengobatan yang meningkatkan risiko trombosis pada penderita kanker diantaranya adalah operasi, kemoterapi dengan obat-obat tertentu seperti cisplatin, asparaginase, thalidomide, maupun terapi hormonal. Kondisi komorbid atau imobilisasi yang sering dialami oleh pasien kanker yang dirawat juga meningkatkan risiko trombosis pada pasien tersebut. Selain itu, pemakaian kateter vena sentral juga meningkatkan risiko trombosis pada area kateter tersebut.

Syncope as Initial Presentation in an Undifferentiated Type Acute Myeloid Leukemia Patient with Acute Intracranial Hemorrhage

Intracranial hemorrhage (ICH) is a catastrophic complication in patients with acute myeloid leukemia (AML). AML cells, especially in the acute promyelocytic leukemia subtype, may release microparticles (MPs), tissue factor (TF), and cancer procoagulant (CP) to promote coagulopathy. Hyperfibrinolysis is also triggered via release of annexin II, t-PA, u-PA, and u-PAR. Various inflammatory cytokines from cancer cells, such as IL-1β and TNF-α, activate endothelial cells and promote leukostasis. This condition may increase the ICH risk and lead to poor clinical outcomes. Here, we present a case under a unique situation with acute ICH detected prior to the diagnosis of AML. The patient initially presented with two episodes of syncope. Rapidly progressive ICH was noted in follow-up computed tomography (CT) scans. Therefore, we highlight that AML should be among the differential diagnoses of the etiologies of ICH. Early diagnosis and timely intervention are very important for AML patients.

The effect of cancer procoagulant on expression of metastatic and angiogenic markers in breast cancer and embryonic stem cell lines

Cancer procoagulant is present only in malignant tumours and the undifferentiated tissues of human placenta. Its possible role in angiogenesis and metastasis was investigated. Cancer procoagulant increased the steady-state mRNA level of L1 cell adhesion molecule (L1CAM) in MCF-7 breast cancer cells and E14 mouse embryonic stem cells (MESCs), while an increase in angiogenin mRNA was observed in MDA-MB-231 breast cancer cells. Furthermore, production of vascular endothelial growth factor (VEGF) protein in MCF-7 breast cancer cells and E14 MESCs, but decreased in MDA-MB-231 breast cancer cells. We conclude that cancer procoagulant could potentially play a part in angiogenesis in cancer and vascular development during embryonic development.

Endoprotease Profiling with Double-Tagged Peptide Substrates: A New Diagnostic Approach in Oncology

Background: The measurement of disease-related proteolytic activity in complex biological matrices like serum is of emerging interest to improve the diagnosis of malignant diseases. We developed a mass spectrometry (MS)-based functional proteomic profiling approach that tracks degradation of artificial endoprotease substrates in serum specimens. Methods: The synthetic reporter peptides that are cleaved by tumor-associated endopeptidases were systematically optimized with regard to flanking affinity tags, linkers, and stabilizing elements. Serum specimens were incubated with reporter peptides under standardized conditions and the peptides subsequently extracted with affinity chromatography before MS. In a pilot study an optimized reporter peptide with the cleavage motif WKPYDAADL was added to serum specimens from colorectal tumor patients (n = 50) and healthy controls (n = 50). This reporter peptide comprised a known cleavage site for the cysteine-endopeptidase “cancer procoagulant.” Results: Serial affinity chromatography using biotin- and 6xHis tags was superior to the single affinity enrichment using only 6xHis tags. Furthermore, protease-resistant stop elements ensured signal accumulation after prolonged incubation. In contrast, signals from reporter peptides without stop elements vanished completely after prolonged incubation owing to their total degradation. Reporter-peptide spiking showed good reproducibility, and the difference in proteolytic activity between serum specimens from cancer patients and controls was highly significant (P < 0.001). Conclusions: The introduction of a few structural key elements (affinity tags, linkers, d-amino acids) into synthetic reporter peptides increases the diagnostic sensitivity for MS-based protease profiling of serum specimens. This new approach might lead to functional MS-based protease profiling for improved disease classification.