The Effects of new T cell line derived lymphokines on B cell activation

Sofia Mubarika Haryana -- Pengaruh limfokin yang berasal dari T cell line baru terhadap aktivasi sel B Telah diketahui bahwa untuk aktivasi limfosit B diperlukan faktor pertumbuhan yang disebut limfokin atau sitokin. Banyak bukti menunjukkan bahwa limfosit T yang teraktivasi menghasilkan substansi yang dapat memacu proliferasi atau diferensiasi limfosit B. Dewasa ini telah dapat diidentifikasi berbagai limfokin yang disebut sebagai interleukin (IL) seperti IL-2, IL-3, IL-4, IL-5, IL-6 dan IL-7 yang ikut berperan dalam aktivasi sel B. Namun, mekanisme aktivasi sel B oleh limfokin sampai sekarang masih terus berkembang dan dipelajari. Untuk dapat lebih memahami aktivasi sel B, dalam penelitian ini telah dilakukan pembuatan suatu T cell line, dan telah dikarakterisasi, yakni menunjukkan fenotipe Thyl+, Lyt1+2+, Dalam penelitian ini berbagai aktivator poliklonal lipopolysaccharide (LPS), ConA, dextran sulfat dipakai untuk memacu T cell line menghasilkan limfokin. Aktivitas limfokin pada supernatannya kemudian dianalisis dengan menggunakan blastogenesis assay dengan 3H-thymidine dan hemolytic plaque assay. Hash penelitian menunjukkan bahwa T cell line menghasilkan faktor pertumbuhan yang memacu proliferasi sel B (B cell growth factor II = BCGF II atau IL-5) dan faktor yang memacu sel B untuk berdiferensiasi (B cell differentiating factor = BCDF atau IL- 6) dan menghasilkan igM dan IgG. Key words : blastogenesis assay -- hemolitic plaque assay -- B cell activation -- T cell line -- lymphokine

Long Non-Coding RNA (lncRNA) and MicroRNA ( miRNA) in Cancer Management

AbstractThe discovery of microRNA, a small non coding RNA, has shed light to the dark matters (98%) of the genome. This finding resulted in a Nobel Prize awarded to Fire and Mello in 2006. miRNA a small non coding RNA  which played  a very important role in regulating protein expression through  3”UTR  or other binding places to mRNA target. miRNA have been considered as negative regulators of protein coding gene expression that may impact in cell differentiation, proliferation,  survival and all fundamental cellular processes, also  implicated in carcinogenesis. miRNA can be grouped into tumor suppressor miRNA (miRSuppressor) and oncogenic miRNA (OncomiR). miRSuppressor regulates protein expression through targeting oncogenic mRNA, meanwhile OncomiR target mRNA Tumor Suppressor. Evidence indicates that deregulation in genetic and epigenetic may cause overexpression of oncomiR and loss of expression of Tumor Suppressor miR.  In addition to that, in recent years, evidences showed that cell-to-cell communication conducted via exosome, which is released from every cell in physiological and pathological conditions andconsidered as fingerprints of cell and its status. This is a paramount biomarker discovery in cancer. In subsequent years, a lot of research further performed for the development of new cancer therapy. Our team GenomiR present our preliminary data on several miRNA in cancers aimed to develop minimal invasive biomarkers in cancer. Recently, the long non coding (lnc) RNA, another class of non-coding RNA have also attracted interest from many scientists in the world. lncRNA have emerged as an essential regulator in almost all aspect of biology included carcinogenesis. lncRNA considered as emerging key player in non-coding world.nCRNA (miRNA and lncRNA) in the context of cancer management will be discussed in this presentatio

Selective cytotoxic effects on cancer cell-lines of a protein fraction isolated from annona squamosa and containing ribosome inactivating proteins

A partially-purified protein fraction (PfaI) from Annona squamosa contains ribosome-inactivating protein (RIPs) which cleave supercoiled double stranded DNA and ribosomal RNA. Agents that cleave both DNA or RNA have potential anti-cancer activity. Pfal was screened against B-LCL EBV/NPC, Myeloma, and Raji cancer cell-lines compared with normal lymphocytes for selective cytotoxic effects. It caused 90% cytotoxity of cancer cells at a concentration of 0.1 gg/mL for B-LCL EBV/NPC and Raji cells and 1.0 ug/L for Myeloma cells. PfaI was much less toxic to normal lymphocytes (20% and 30% cytotoxity at 0.1 and 1.0 pg/mL respectively). Keywords: Annona squamosa â cytotoxicity â ribosome -inactivating proteins â cancer cell- line

Histopatologik dan genetika penyakit alzheimer

Alzheimer\u27s Disease (AD), the most common cause of dementia, has become a major public health concern as cognitive deterioration as well as behavioral, affective and psychotic disturbances. Four different genes have been associated with AD, and others likely to be discovered. This finding made a dramatic progress in understanding the neurogenetics and pathophysiology AD. The mechanism by which altered amyfoid and tau protein metabolism may produce neuronal degeneration in AD are being identified. The neurofibrillary tangles which consist of intraneural bundles of abnormal fillament, composed of a highly phosphorylated form of microtubule - associated protein tau which occupying the perikaryotic cytoplasm and extending to the dendritic processes. Cellular and molecular approaches have been done to detect proteins from many materials : cerebrospinal fluid, serum, tissues which is likely could be used as diagnostic and peripheral markeri.e western blot, immunohistochemistry using specific monoclonal antibodies. Some gen abnrmallities i.e. mutations could be detected by PCR method in APP gene, PS 1 dan PS 2 genes, also allelic by homozygocity/ heterozygocity of APOE gene, which can give clue what are happening in those genes of AD. Based on these discoveries, rational therapeutic strategies are developing rapidly. Because cholinergic dysfunction may contribute understanding to the symptom of AD patients, enhancing cholinergic neurotransmission constitutes a rational basis for symptomatic treatment. Cholinergic enhancement with acetylcholine esterase inhibitor has now been shown to provide mild symptomatic benefit. Anti inflammatory and antioxidant, neurotransmitter modulation and neuroprotection may also directly interfere with underlying process. Key words : Alzheimer\u27s Disease (AD) - four genes defects - patophysiology - treatmen

Imunologi Aids

ABSTRAK AIDS is caused by infection of HIV with manifestation of immune deficiency syndrome. Virus protein antigen env gp120 tends to bind CD4 molecules express on Th cells, monocy tes and other CD4-cells. It has been shown that Th cells dominantly suffered from infect-ion since CD4 molecules express mostly on Th cells. The virus has the capability to destroy the CD4\u27 cells (cytopha tic) since Th cells is the central regulator of immune respons of the body, that many cells correlated to immune system will also be affected such as B cells, NK cells and other T cell subpopulations. The most characteristic feature is the decrease number and function of CD4 helper/inducer T lymphocytes. Patients with HIV infection also have abnormalities in the number and activity of CDS suppressor /cytotoxic T lymphocytes, defective soluble antigen recognition, polyclonal B cell activation and decreased cytotoxicity. The CD4 cell defect is the most critical abnormality in the immwiopa thogenesis of HIV. Key Words : AIDS, HIV, gp 120, CD4- Th, immune regulatio

MiR-21 and mRNA PTEN Expression Levels and Biomarker Potential in Breast Cancer

MiR-21 has been linked to tumorigenesis, development, and metastasis in tumor pathogenesis. All human cancers, including breast cancer, have increased expression of MiR-21, which is the only miRNA that has increased expression. PTEN expression was found to be reduced in the majority of solid tumors, including breast cancer. Since lymph node metastatic factors, estrogen receptor status, tumor grade, and tumor node metastasis (TNM) all decreased PTEN expression, the PTEN expression profile may be a very useful prognostic marker in breast cancer. PTEN inhibits PIP3 (phosphatidylinositol 3,4,5-triphosphate) activity by having protein phosphatase and lipid phosphatase activity that is the polar opposite of PI3K (Phosphatidyl Inositol 3-Kinase). The aim of this research was to see how often miR-21 and mRNA PTEN were expressed at different stages of breast cancer and whether they could be used as prognostic markers. This type of research is an observational study with a cross-sectional design. The sample size of 43 people came from breast cancer patients. Analysis of miR-21 expression and mRNA PTEN using Real-Time qPCR. The results showed that miR-21 expression increased 1.32 times at an advanced stage compared to an early stage, while mRNA PTEN expression decreased 1.33 fold at an advanced stage compared to an early stage. According to the findings, miR-21 expression in the blood plasma of breast cancer patients was upregulated at an advanced stage compared to an early stage and downregulated mRNA PTEN expression. MiR-21 which is increased at an advanced stage has the potential to be a poor prognostic marker at the stage of breast cancer. The change in miR-21 expression can be a good candidate as a molecular prognostic marker and for future research the role of miR-21 in breast cancer progression will further enrich the scientific repertoire, especially in the health and clinical fields

Treatment options for Indonesian triple negative breast cancer patients: a literature review of current state and potentials for future improvement

 Triple negative breast cancer (TNBC) is still associated with grave prognosis, especially compared to other breast cancer subtypes. Advances in medical science have improved our understanding on the biological nature and heterogeneity of TNBC, explaining the efficacy variability of existing chemotherapeutic drugs on TNBC patients. Complexity of TNBC has led to wide variation of TNBC treatment across the globe, resulting in unsatisfactory treatment outcome. This issue is further complicated by the absence of TNBC treatment guideline in many countries, including in Indonesia. This review discusses systemic treatment options for TNBC while taking account its molecular heterogeneity. Specific consideration is made for Indonesia, not only for current clinical practice, but also for future improvements. Immunotherapy, especially programmed cell death 1 (PD-1/PD-L1) inhibitor, has recently shown promising result in TNBC patients. It can be concluded that TNBC is heterogenous and treatment option should be tailored based on its molecular profile

Synergistic effects of para-hydroxy meta-methoxy chalcone (pHmMC)- doxorubicin treatments on T47D breast cancer cells

Resistance to some cancer chemotherapeutic drugs has been identifed. One strategy to overcome that problem is by combining two or more of the drugs to get co-chemotherapeutic effects. A derivate chalcone, 3 - (4’-hydroxy-3’-methoxyphenyl)-1-phenyl-2-propene-1-on or para hydroxy meta methoxy chalcone (pHmMC), has been reported to have cytotoxic activity on some cancer cells through some pathways. The aim of this study was to investigate the effects of combinations of pHmMC and Doxorubicin (Dox) on the cytotoxicity, anti-proliferation, apoptosis, and the cell cycle of T47D (breast cancer cell-lines) in vitro. The cytotoxic and antiproliferative activity were determined by MTT (3-[4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] assay. The combination index (CI) was used to determine the synergistic, additive or antagonistic effects of the combinations. Flowcytometry method was performed to determine the combination effects on the apoptosis and cell cycle. The results indicated that the combinations had a higher inhibitory effect on the cell growth compared to those of single treatments of pHmMC and Dox. All the doses used in the combinations were lower of the single doses at their IC50s. The results showed all the combinations gave synergistic (CI: 0.3 – 0.7) up to strong synergistic (CI: 0.1 – 0.3) effects. The synergistic effects of the combinations were due to increased apoptosis and induced cell cycle arrest in S and G2/M phases on the cancer cell lines

IN SILICO MOLECULAR DOCKING OF XANTHONE DERIVATIVES AS CYCLOOXYGENASE-2 INHIBITOR AGENTS

Objective: To demonstrate the potential ofdifferent xanthone derivatives as cyclooxygenase-2 (COX-2) inhibitor agents and their selectivity against cycloooxygenase-1 (COX-1) and COX-2 using molecular simulation.Methods: Nine novel xanthone derivatives (compounds A-I) were employed to dock against protein COX-2 (Protein Data Bank/PDB ID: 1CX2) and COX-1 (PDB ID: 3N8Z). Celecoxib, a selective COX-2 inhibitor, was chosen as a control compound. The free binding energy produced by the docking was scored using Protein-Ligand Ant System (PLANTS) and the hydrogen bonds (H-bonds) between ligands and enzymes were visualised using Pymol.Results: Molecular docking studies revealed that celecoxib docked to the active site of COX-2 enzyme, but not to COX-1; whereasxanthone derivatives docked to the active site of both COX-2 and COX-1. Free binding energy of xanthone derivatives ranged between-73,57 to-79,18 and between-73,06 to-79,25 against COX-2 and COX-1, respectively, and-78,13 against celecoxib. H-bonds in the molecule of xanthone derivatives and COX-2 protein were found in amino acid residues Arg120, Tyr355, Tyr385,and Ser353. There was an insignificant difference between the free binding energyof xanthone derivatives against COX-2 and against COX-1, suggesting that their inhibition was non-selective.Conclusion: In conclusion, in silico studies showed that xanthone derivatives could be effective as potential inhibitors against COX-2, although they are not selective

In. Vitro cleavage of supercoiled double stranded dna by crude extract of Annona squamosa L.: Pemotongan dna superkoil untai ganda secara in vitro oleh eks7\u27rak

The ability of cleaving, supercoiled double stranded DNA has recently been found in several ribosome-inactivating proteins (RIP), a group of toxic proteins produced in plants, such as: trichosantin from Trichosanthes kirilowil, ricin from Ricinus communis and pokeweed antiviral protein (PAP) from Phytalocca americana. This potent activity makes them excellent candidates as the toxic part of immunotoxin for cancer therapy. The supercoiled DNA cleaving activity was used to identify the presence of RIP in Annona squamosa, a plant which has been traditionally used to prevent pregnancy. Results showed that the crude extract of A.squamosa seeds expressed enzymatic activity to cleave supercoiled double stranded DNA into a nick circular conformation at low concentrations. Incubation at high concentration indicated that supercoiled DNA was cleaved into a linear form. However, it had no effect on a linear DNA. It can be concluded that A. squamosa seeds contains RIP-like protein. Key word : Ribosome-inactivating protein (RIP), Annona squamosa L. ABSTRAK Kemampuan untuk memotong DNA superkoil untai ganda secara in-vitro akhir-akhir ini diketahui dimilild oleh beberapa ribosome-inactivating protein (RIP), yakni sekelompok protein toksik yang dihasilkan °felt beberapa tanaman, seperti: trichosantin yang berasal dad tanaman Trichosanthes kirilowii, ricin dari Ricinus communis dan pokeweed antiviral protein (PAP) dad Phytalocca americana. Aktivitas ini Akan dapat menjadikan RIP sebagai ujung toksik dari suatu immunotoksin untuk pengobatan penyakit kanker Aktivitas memotong DNA superkoil ini digunakan untuk menguji adanya kandungan RIP dalam Annona squamosa, yakni tanaman yang secara tradisional telah digunakan sebagai pencegah kehantilan. Hasil yang diperoleh menunjukkan bahwa ekstrak gubal A.squamosa mernpunyai aklivitas memotong DNA superkoil memjadi bentuk nik sirkuler pada kadar rendah. Inkubasi pada kadar yang tinggi menunjukkan bahwa, DNA superkoil terpotong menjadi bentuk hniemya. Akan tetapi hal ini tidak berefek terhadap DNA tinier. Sehingga dapat disimpulkan bahwa A.squamosa mengandung suatu protein sejenis RIP. Kata kunci : Ribosome-inactivating protein (RIP), Annona squamosa