Circulating miR-10b, soluble urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 as predictors of non-small cell lung cancer progression and treatment response.

BACKGROUND: Despite advances in lung cancer treatment, most lung cancers are diagnosed at an advanced stage. Expression of microRNA10b (miR-10b) and fibrinolytic activity, as reflected by soluble urokinase-type plasminogen activator receptor (suPAR) and plasminogen activator inhibitor 1 (PAI-1), are promising biomarker candidates. OBJECTIVE: To assess the expression of miR-10b, and serum levels of suPAR and PAI-1 in advanced stage non-small cell lung cancer (NSCLC) patients, and their correlation with progression, treatment response and prognosis. METHODS: The present prospective cohort and survival study was conducted at Dharmais National Cancer Hospital and included advanced stage NSCLC patients diagnosed between March 2015 and September 2016. Expression of miR-10b was quantified using qRT-PCR. Levels of suPAR and PAI-1 were assayed using ELISA. Treatment response was evaluated using the RECIST 1.1 criteria. Patients were followed up until death or at least 1 year after treatment. RESULTS: Among the 40 patients enrolled, 25 completed at least four cycles of chemotherapy and 15 patients died during treatment. Absolute miR-10b expression ⩾ 592,145 copies/µL or miR-10b fold change ⩾ 0.066 were protective for progressive disease and poor treatment response, whereas suPAR levels ⩾ 4,237 pg/mL was a risk factor for progressive disease and poor response. PAI-1 levels > 4.6 ng/mL was a protective factor for poor response. Multivariate analysis revealed suPAR as an independent risk factor for progression (ORa⁢d⁢j, 13.265; 95% confidence intervals (CI), 2.26577.701; P= 0.006) and poor response (ORa⁢d⁢j, 15.609; 95% CI, 2.221-109.704; P= 0.006), whereas PAI-1 was an independent protective factor of poor response (ORa⁢d⁢j, 0.127; 95% CI, 0.019-0.843; P= 0.033). CONCLUSIONS: Since miR-10b cannot be used as an independent risk factor for NSCLC progression and treatment response, we developed a model to predict progression using suPAR levels and treatment response using suPAR and PAI-1 levels. Further studies are needed to validate this model.

Draft Genome Sequence of the Marine-Derived, Anticancer Compound-Producing Bacterium Streptomyces sp. Strain GMY01.

The marine Streptomyces sp. strain GMY01 was isolated from Indonesian marine sediment. Genome mining analysis revealed that GMY01 has 28 biosynthetic gene clusters, dominated by genes encoding nonribosomal peptide synthetase and polyketide synthase.

Circulation EBV Mir-Bart-7 Relating to Clinical Manifestation in Nasopharyngeal Carcinoma.

OBJECTIVE: Nasopharyngeal Carcinoma (NPC) is an endemic head and neck malignancy in Asia Pacific regions that is associated with chronic infection by Epstein-Barr virus (EBV). EBV miR-BART-7 is a microRNA (miRNA) encoded by EBV that regulates malignant behavior of NPC. However, the role and function of miR-BART7 are not clear, particularly the relation of circulating levels and patient's clinical presentation. METHODS: Circulating miR-BART-7 levels were measured by using qRT-PCR and were correlated with clinical and pathological data. RESULT: Of 52 NPC patients included in this study, 85% were diagnosed in the late stages (Stage III-IV). 73% of tumors were non-keratinizing undifferentiated NPC, 92% of tumors were WHO class III histology and all cases were EBV-IgA positive. Over-expression of miR-BART7-3p was correlated with positive regional lymph nodes in newly diagnosed (4.61 fold changes, p <0.05). CONCLUSION: Over-expression of circulating EBV miR-BART7 correlated with positive regional lymph nodes reflecting the diagnostic and prognostic values of circulating miR-BART7 for patients with NPC.

Anti-Proliferative Activity and Apoptosis Induction of an Ethanolic Extract of Boesenbergia pandurata (Roxb.) Schlecht. against HeLa and Vero Cell Lines.

Rhizomes of Boesenbergia pandurata (Roxb.) Schlecht have been reported to contain active compounds with anticancer properties. This research was carried out to examine anti-proliferative and apoptotic induction against HeLa and Vero cells-line. Dried powder of B. pandurata rhizomes was extracted by a maceration method using 90% ethanol. Cytotoxic assays to determine IC50 and anti-proliferative effects were carried out by MTT methods. Observation of apoptosis was achieved with double staining using acridine orange and ethidium bromide. The results showed that ethanolic extract of B. pandurata was more cytotoxic against HeLa cells (IC50 of 60 µg/ mL) than Vero cells (IC50 of 125 µg/mL). The extract had higher anti-proliferative activity as well as apoptotic induction in HeLa than Vero cells. Therefore, it was concluded that the ethanolic extract of B. pandurata had anti-proliferative as well as apoptosis induction activity dependent on the cell type.

Expression of interleukin-8, interleukin-10 and Epstein-Barr viral-load as prognostic indicator in nasopharyngeal carcinoma.

Interleukin-8 (IL-8) is angiogeneic chemokine that plays a potential role in both development and progression of many human malignancies including nasopharyngeal carcinoma (NPC). Epstein- Barr virus (EBV) is recognized to be an important etiologic agent of NPC as the viral gene products are frequently detected in NPC tissue along with the elevation of antibody titre to the viral protein (VCA-p18+ EBNA1) of IgA in the majority of patients. Elevated plasma of Viral Load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum /plasma parameters such as the level of certain interleukins (IL-8 and IL-10) has also been implicated in NPC progression. The study aimed to investigate the correlations between plasma Viral Load and the level of interleukin (IL-8) and Interleukin (IL-10) in relating these parameters to the stages of NPC. In addition of Viral Load (VCA-p18+EBNA1) IgA, Interleukin-8 and Interleukin-10 before and after therapy will be investigated to seek the possible marker for disease progression. A total of 39 NPC patients and 29 healthy control individuals enrolled in this study. Plasma Viral Load was quantified using real-time quantitative PCR. The Level of plasma interleukins both IL-8 and IL-10 were analyzed using ELISA methods. Results indicated there was a significant decrease in viral load was detected in plasma of NPC patients following therapy. Plasma of viral load was shown to be a good prognosticator for disease progression. There were positive correlation between plasma of viral load and IL-8. These non invasive parameters expressed in blood, could be substitutes of viral load using brushing method, which is invasive. In conclusion that: Viral Load, (VCA-p18+EBNA1) IgA and IL-8 levels are promising markers for the presence of NPC and progression of the disease.

Methylation status and immunohistochemistry of BRCA1 in epithelial ovarian cancer.

BACKGROUND: Cancer initiation and progression are controlled by genetic and epigenetic events. One epigenetic process which is widely known is DNA methylation, a cause of gene silencing. If a gene is silenced the protein which it encodes will not expressed. OBJECTIVES: 1. Identify the methylation status of BRCA1 in patients with epithelial ovarian cancer (EOC)and assess BRCA1 protein expression in tumor tissue. 2. Examine whether BRCA1 gene methylation and BRCA1 protein are associated with survival of epithelial ovarian cancer patients. METHODS: The study design was a prospective-cohort study, conducted at Sardjito hospital, Yogyakarta, Indonesia. RESULTS: A total of 69 cases were analyzed in this study. The data showed that the methylation status of BRCA1 in EOC was positive in 89.9%, with clear protein expression of BRCA1 in 31.9%. Methylation status and expression of BRCA1 were not prognosticators of EOC patients. Menarche, CA125 level, clinical stage and residual tumor were independent factors for prognosis.

Association Between High Serum Matrix Metalloproteinase-9 and MMP-9 (-1562C>T) Polymorphism in Patients With ST-Elevation Acute Myocardial Infarction.

BACKGROUND: Matrix metalloproteinase (MMP)-9 is excessively expressed in frail region of atherosclerotic plaque and released in circulation following plaque rupture. High MMP-9 level associated with severity of occluded thrombus and subsequent myocardial infarction. MMP-9 (-1562C>T) polymorphism associated with acute myocardial infarction, however conflicting data present regarding impact of MMP-9 (-1562C>T) polymorphism on circulating MMP-9 level in acute myocardial infarction with ST-elevation (STEMI), clinical entity represents totally occluded coronary thrombus. METHODS: We enrolled consecutively subjects with acute coronary syndrome treated in intensive coronary care unit. Acute coronary syndrome diagnosis were classified into STEMI and non-ST-elevation acute coronary syndrome (NSTEACS). Seventy consecutive subjects were enrolled for this study, 31 subjects with STEMI and 39 subjects with NSTEACS. RESULTS: On admission serum MMP-9 level, measured with sandwich enzyme immunoassay, were higher in STEMI as compared with NSTEACS (1,574.2 ± 604.1 ng/mL vs. 1,104.4 ± 591.5 ng/mL, P < 0.01). Proportion of subjects with MMP-9 (-1562C>T) polymorphism, analyzed with PCR-RFLP, were higher in STEMI as compared with NSTEACS (66.7% vs. 33.3%, P = 0.15). T allele frequency was almost twice in STEMI as compared to in NSTEACS. Almost all (83%) subjects with MMP-9 (-1562C>T) polymorphism had high serum MMP-9 level (> 1,334.5 ng/mL) during STEMI, whereas in NSTEACS all subjects had low level. CONCLUSION: MMP-9 (-1562C>T) polymorphism associated with high serum MMP-9 level in patients with STEMI.

LMP1 and LMP2 may be prognostic factors for outcome of therapy in nasopharyngeal cancers in Indonesia.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy that is invasive and metastasizes easily. In several Asian countries it is the most commonly found of the head and neck malignancies. Epstein Barr virus (EBV) infection is one of the agents causing NPC, so that expression of LMP1 and LMP2 may affect the outcome of therapy, metastasis, recurrence, and survival of NPC patients. This study aimed to investigate their expression in relation to therapy outcome and survival in a series of Indonesian NPC patients. The methods used were nested case control and Kaplan-Meier survival analysis. Differences in therapy outcome in relation to LMP1 and LMP2 expression were analyzed through chi square statistics. As a result, in post treatment NPC, there was a significant difference in therapy outcome between LMP2+ compared to LMP2⁻ (P = 0.001). There was also a significant difference in 24-months-survival between NPCs expressing LMP1+ or LMP2+ compared to those expressing LMP1⁻ or LMP2⁻.