Niveles plasmáticos de midkina en pacientes con trastorno por uso de cocaína en abstinencia / Plasma midkine levels in patients with cocaine use disorder during abstinence

Diversos estudios preclínicos han sugerido que la midkina endógenapodría jugar un papel modulador clave sobre los efectos neurotóxicosy adictivos de distintas drogas, incluidos los psicoestimulantes. Estahipótesis no ha sido aún explorada en humanos. Como primer pasoen esta dirección, en el presente trabajo hemos medido los nivelesplasmáticos de midkina en 75 pacientes con trastorno por uso decocaína en abstinencia y 26 controles apareados con los anteriorespor sexo, edad e índice de masa corporal. Los pacientes fueronademás divididos en un grupo de abstinencia temprana (menos deun mes, n = 30) y otro de abstinencia tardía (más de un mes, n =45). Se cuantificaron los niveles plasmáticos de midkina de todoslos participantes mediante un ensayo por inmunoabsorción ligadoa enzimas. Los pacientes en abstinencia temprana mostraron unincremento del 60% en su concentración plasmática de midkina conrespecto a los controles que tendió a desaparecer en los pacientes conperiodos de abstinencia más prolongados. Los resultados demuestranque los niveles periféricos de midkina están estrechamenterelacionados con el uso de cocaína y apoyan la idea de que dichacitoquina podría jugar un papel protector limitando la actividadbiológica de los psicoestimulantes. (AU)

Preclinical evidence suggests that endogenous midkine couldplay a key modulatory role on the neurotoxic and addictive effectsof different kinds of drugs of abuse, including psychostimulants.However, this hypothesis has not yet been explored in humans. As afirst approach to progress in this knowledge, we have comparativelystudied plasma midkine levels in 75 patients with cocaine use disorderunder abstinence and 26 control subjects matched for sex, ageand body mass index. Patients were further segmented into earlyabstinent (up to one month of abstinence, n = 30) and late-abstinent(more than one month of abstinence, n = 45). Midkine levels werequantified in plasma samples of all the participants by enzyme-linkedimmunosorbent assays. Early-abstinent patients exhibited a 60%increase of midkine plasma concentration in comparison with thecontrols. This elevation tended to normalize upon the progressionof abstinence. The results obtained demonstrate that peripheralmidkine levels are closely related to cocaine use and are consistentwith the idea that this cytokine could play a protective role by limitingthe biological activity of psychostimulants. (AU)

Diagnostic performance of Midkine ratios in fine-needle aspirates for evaluation of Cytologically indeterminate thyroid nodules.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a basic diagnostic tool for thyroid nodules. However, 15-30% of nodules are cytologically indeterminate. Midkine (MK), a pleiotropic growth factor, is often upregulated in patients with cancers. This study aimed to evaluate the role of MK and its ratios in fine-needle aspirates (FNA) for predicting thyroid malignancy. METHODS: This retrospective study included patients with thyroid nodules who underwent preoperative FNA and/or thyroidectomy between April 2017 and September 2017. MK levels in FNA washout were measured by enzyme-linked immunosorbent assay, and thyroglobulin (TG) and free thyroxine (FT4) levels in FNA washout were measured by chemiluminescent immunometric assays. RESULTS: A total of 217 patients with 242 nodules were included in this study. The concentrations of TG, FT4, MK/TG, MK/FT4, and FT4/MK were significantly different between papillary thyroid carcinomas and benign thyroid nodules. Both MK/TG and MK/FT4 ratios were positively correlated with maximum tumor diameter, extrathyroidal extension, and T and N stages. The area under the curve for MK/TG was 0.719 with a cutoff value of 55.57 ng/mg, while the area under the curve for MK/FT4 was 0.677 with a cutoff value of 0.11 µg/pmol. FNAC in combination with MK/FT4 had a higher sensitivity (95% vs. 91%) and accuracy (96% vs. 92%) than FNAC alone for cytologically indeterminate specimens, those of unknown significance, or those suspected of malignancy. CONCLUSIONS: MK/FT4 and MK/TG may have diagnostic utility for evaluation of papillary thyroid carcinomas, particularly for cytologically indeterminate thyroid nodules.

Comparison of diagnostic accuracy of Midkine and AFP for detecting hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Midkine (MDK) has been proposed as one of the most promising markers for hepatocellular carcinoma (HCC). This meta-analysis was conducted to compare the diagnostic accuracy of MDK and α-fetoprotein (AFP) for HCC. METHODS: We systematically searched PubMed/MEDLINE, Ovid/EMBASE, and the Cochrane Library for all relevant studies up to 18 May 2019. The Revised Quality Assessment for Studies of Diagnostic Accuracy tool (QUADAS-2) was used to assess the methodological quality of the included studies. The sensitivity, specificity, and the area under the curve (AUC) of MDK and AFP for detecting HCC were pooled using random-effects model. RESULTS: Seventeen studies from five articles with a total of 1122 HCC patients and 2483 controls were included. The summary estimates using MDK and AFP for detecting HCC were as follows: sensitivity, 85 vs 52%, specificity, 82 vs 94%, and AUC, 0.90 vs 0.83. The summary estimates using MDK and AFP for detecting hepatitis virus-related HCC as follows: sensitivity, 93 vs 74%, specificity, 85 vs 97%, and AUC, 0.95 vs 0.97. The summary estimates using MDK and AFP for detecting early-stage HCC were as follows: sensitivity, 83.5 vs 44.4%, specificity, 81.7 vs 84.8%, and AUC, 0.87 vs 0.52. The summary estimates using MDK for detecting AFP-negative HCC as follows: sensitivity, 88.5%, specificity, 83.9%, and AUC, 0.91. CONCLUSION: MDK is more accurate than AFP in diagnosing HCC, especially for early-stage HCC and AFP-negative HCC. Both MDK and AFP had excellent diagnostic performance for hepatitis virus-related HCC.

Midkine (MDK) growth factor: a key player in cancer progression and a promising therapeutic target.

Midkine is a heparin-binding growth factor, originally reported as the product of a retinoic acid-responsive gene during embryogenesis, but currently viewed as a multifaceted factor contributing to both normal tissue homeostasis and disease development. Midkine is abnormally expressed at high levels in various human malignancies and acts as a mediator for the acquisition of critical hallmarks of cancer, including cell growth, survival, metastasis, migration, and angiogenesis. Several studies have investigated the role of midkine as a cancer biomarker for the detection, prognosis, and management of cancer, as well as for monitoring the response to cancer treatment. Moreover, several efforts are also being made to elucidate its underlying mechanisms in therapeutic resistance and immunomodulation within the tumor microenvironment. We hereby summarize the current knowledge on midkine expression and function in cancer development and progression, and highlight its promising potential as a cancer biomarker and as a future therapeutic target in personalized cancer medicine.

Clinical value of jointly detection pleural fluid Midkine, pleural fluid adenosine deaminase, and pleural fluid carbohydrate antigen 125 in the identification of nonsmall cell lung cancer-associated malignant pleural effusion.

BACKGROUND: Midkine (MK) level has been shown to be elevated in serum of patients with nonsmall cell lung cancer (NSCLC). However, the diagnostic value of MK in pleural effusion in NSCLC has not been well validated and established. METHODS: Samples of NSCLC-associated malignant pleural effusions (MPE) and benign effusions (BPE) were collected. The pleural fluid MK (pMK), pleural fluid adenosine deaminase (pADA), pleural fluid lactate dehydrogenase (pLDH), pleural fluid glucose (pGLU), pleural fluid ferritin (pFER), pleural fluid CA199 (pCA199), pleural fluid CA125 (pCA125), pleural effusion white cell count (pWBC), and pleural effusion red cell count (pRBC) were analyzed, and the clinical data of each group were collected for statistical analysis. RESULT: The level of pMK, pCA125, pMK + pCA125, and pMK + pCA125 + pADA in the MPE was significantly higher than the BPE group (P = .003, .000, .000, .000). The pADA level in the BPE was significantly higher than the MPE group (P = .003). It showed that the area under the ROC curve (AUC) (0.816) of jointly detection pMK, pCA125, and pADA was significantly higher than other markers for the diagnosis of MPE. Therefore, joint detection of pMK + pCA125 + pADA suggested that the sensitivity, specificity, and AUC was 82.54%, 74.19% at the cutoff 0.47 and diagnostic performance was higher than others. CONCLUSION: Joint detection of pMK + pCA125 + pADA can be used as a good indicator for the identification of MPE of NSCLC.