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Abstrak :
ABSTRAK Latar Belakang: Leukemia mieloid akut (LMA) mempunyai karakteristik heterogenisitas derajat tinggi yang ditandai dengan kelainan kromosom/sitogenetik, mutasi gen, dan perubahan eskpresi gen. Mutasi gen telah diketahui mempunyai peran penting sebagai biomarker prognostik dan prediktif terkait dengan kesintasan, dan juga sebagai sasaran terapi. Mutasi gen yang terlibat cukup penting dalam prognosis pasien LMA adalah FLT3-ITD, NPM1, dan CEBPA. Tujuan: Untuk mengetahui frekuensi imunofenotip, mutasi gen FLT3-ITD, NPM1, dan CEBPA serta untuk mengetahui hubungannya dengan kesintasan tiga bulan pada pasien LMA. Metode Penelitian: Penelitian dilakukan dengan menggunakan desain longitudinal prospektif terhadap pasien LMA dewasa rawat jalan dan rawat inap RS Kanker Dharmais (RSKD) pada bulan Juli 2014 sampai Februari 2015. Sampel berupa 20 mL aspirat sumsum tulang atau darah perifer dengan antikoagulan EDTA. Penelitian dilakukan di Laboratorium Patologi Klinik dan Bagian Penelitian dan Pengembangan RSKD. Deteksi mutasi gen FLT3-ITD dilakukan dengan metode elektroforesis. Deteksi mutasi NPM1 dan CEBPA dilakukan dengan metode DHPLC yang kemudian dilanjutkan dengan pemeriksaan sekuens DNA untuk mengetahui jenis mutasi. Variabel bebas berupa usia, jenis kelamin, jumlah leukosit, ekspresi imunofenotip (CD34 dan aberrant), dan mutasi gen (FLT3-ITD, NPM1, dan CEBPA), sedangkan variabel tergantung adalah luaran klinis kesintasan dalam tiga bulan. Hasil Penelitian dan Pembahasan: Didapatkan total 66 subjek dengan rerata usia relatif lebih muda yaitu 42,37 + 15,75 dan sebanyak 83,3 % di bawah 60 tahun. Sebanyak 54 % subjek mempunyai ekspresi CD34, dan hanya 15,2 % mempunyai ekspresi aberrant. Terdapat 40 subjek yang menjalani kemoterapi induksi (60,5 %). Hanya 37 dari 66 subjek yang dilakukan pemeriksaan mutasi gen FLT3-ITD, NPM1, dan CEBPA. Frekuensi mutasi gen FLT3-ITD, NPM1 dan CEBPA berturut-turut 16,2 %, 40,5 %, dan 35,1 %. Pada keseluruhan subjek (n = 66) ditemukan bahwa FLT3 wild type dan CEBPA mutasi berhubungan bermakna terhadap kesintasan dalam tiga bulan yang lebih pendek dengan adjusted RR berturut-turut 2,21 (p 0,022; IK95 % 1,50 - 3,26) dan 2,08 (p 0,036; IK95% 1,06 - 4,07). Pada kelompok subjek yang mendapat kemoterapi (n = 40), hanya mutasi FLT3-ITD yang secara klinis mempunyai kecenderungan memengaruhi kesintasan tiga bulan dengan RR 1,73 (p 0,273; IK95 % 1,18 - 2,54). Sebagai hasil tambahan, ditemukan bahwa mutasi NPM1 berhubungan dengan ekspresi CD34 negatif (p 0,018) dan mutasi CEBPA berhubungan dengan jumlah leukosit lebih besar dari 50 x103/μL (p 0,028). Kesimpulan: Usia LMA di Indonesia relatif lebih muda. Frekuensi mutasi FLT3-ITD relatif lebih rendah dan mutasi NPM1 dan CEBPA cenderung lebih tinggi. FLT3 wild type dan mutasi CEBPA berhubungan dengan kesintasan yang lebih pendek pada penelitian ini. Diperoleh data bahwa kejadian mutasi NPM1 behubungan dengan CD34 negatif dan mutasi CEBPA berhubungan dengan jumlah leukosit yang lebih tinggi.

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ABSTRACT Background: Acute Myeloid Leukemia (AML) has high degree of heterogeneity characteristic signed with chromosome/cytogenetic abnormality, gene mutation, and gene expression changes. The importance of gene mutation has been known as prognostic and predictive biomarker associated with survival and also as a targeted therapy. Gene mutation that is considered important in AML patient prognosis are FLT3-ITD, NPM1 and CEBPA. Purpose: To obtain frequency data of immunophenotype and gene mutation of FLT3-ITD, NPM1, and CEBPA, and its relationship with three-month overall survival. Method: This research was a prospective longitudinal study on adult AML patients who were admitted as outpatient and inpatient in Dharmais National Cancer Center (DNCH) on July 2014 until February 2015. Samples used were 20 mL of bone marrow aspirate or peripheral blood using EDTA anticoagulant. Research was done in Pathological Laboratory and Research and Development of DNCH. FLT3-ITD gene mutation was detected using electrophoresis and NPM1 and CEBPA mutation was detected using DHLPC method continued with DNA sequencing examination to know the type of mutation. The independent variables were age, sex, leukocyte, immunophenotype (CD34 and aberrant), gene mutations (FLT3-ITD, NPM2 and CEBPA). The dependent variable was three-months overall survival. Result and Discussion: a total of 66 subjects were collected with mean age relatively young, 39.78 years and 83.3 % of them were under 60 years. Fifty four percent subjects had positivity in CD34 expression and 15.2 % had aberrant expression. Forty subjects received induction chemotherapy (60.5 %). Only 37 of 66 subject were analyzed gene mutations. The frequency of FLT3, NPM1 and CEBPA mutation frequency was subsequently 16.2 %, 40.5 % and 35.1 %. From all subjects (n = 66), was found that wild type FLT3 and mutant CEBPA was statistically significant had twice mortality rate in three months than mutant FLT3-ITD (p 0,022; adjusted RR 2,21; IK95 % 1,50 - 3,26) and wild type CEBPA (p 0,036; adjusted RR 2,08; IK95 % 1,06 - 4,07). In treated groups (n = 40), there was no statistically significant association between independent variables with three-months survival. However, there was a clinically significant tendency that wild type FLT3 was consistently related with longer OS (RR 1.73, 95 % CI 1.18 - 2.54). As an additional result, it was found that the NPM1 mutation is associated with lack of CD34 expression (p 0.018) and CEBPA mutations were associated with leukocyte levels > 50 X103 / mL (p 0.028). Conclusion: The age of AML patients in Indonesia are relatively younger. Proportion of FLT3-ITD gene mutation is relatively lower, whereas proportion of NPM1 and CEBPA mutations tend to be higher. FLT3-ITD wild type and CEBPA mutation are related with shorter survival in this research. Incidence of NPM1 gene mutation is related to lack of CD34 and CEBPA mutation is related to higher leukocyte count.

Abstrak :
ABSTRAK
Kanker paru berkaitan dengan prognosis yang buruk. Oleh karenanya, diperlukan penanda sirkulasi untuk memprediksi respons terapi dan prognosis. Ekspresi mikroRNA 10b miR-10b dan aktivitas fibrinolitik, sebagaimana dicerminkan oleh soluble urokinase-type plasminogen activator receptor suPAR dan plasminogen activator inhibitor 1 PAI-1 , merupakan kandidat biomarker yang menjanjikan.Penelitian ini bertujuan mengevaluasi peran ekspresi miR-21, miR-10b, kadar suPAR dan PAI-1 plasma sebagai prediktor progresi dan respons terapi pada pasien kanker paru stadium lanjut.Penelitian ini merupakan studi kohort dan kesintasan di RS Kanker Dharmais RSKD , Jakarta. Subjek penelitian adalah pasien kanker paru karsinoma bukan sel kecil KPBBSK yang didiagnosis antara bulan Maret 2015 dan September 2016. Ekspresi miR-21 dan miR-10b dikuantifikasi dengan metode real-time polymerase chain reaction RT-PCR . Kadar suPAR dan PAI-1 diperiksa dengan metode enzyme-linked immunosorbent assay ELISA . Respons terapi dievaluasi berdasarkan kriteria RECIST 1.1. Pasien ditindaklanjuti sampai meninggal atau satu tahun setelah terapi.Terdapat 40 pasien yang dilibatkan dalam studi; 25 orang menyelesaikan sedikitnya4 siklus kemoterapi dan 15 lainnya meninggal selama terapi. Ekspresi miR-21 tidak berhubungan dengan progresi atau respons terapi. Kadar absolut miR-10b >592,145 copies/mL atau FC miR-10b > 0.066 bersifat protektif terhadap progresi dan respons buruk, sedangkan kadar suPAR > 4,237 pg/mL merupakan faktor risiko progresi dan respons buruk. Oleh karena dianggap penting, FC miR-10b juga dimasukkan dalam model prediksi progresi. Kadar PAI-1 > 4,6 ng/mL merupakan faktor protektif untuk respons buruk. Kadar suPAR merupakan faktor risiko independen untuk progresi dan respons buruk, sedangkan kadar PAI-1 merupakan faktor protektif independen untuk respons buruk.Simpulan: Model prediksi untuk progresi dapat dibuat dari ekspresi relatif miR-10b dan kadar suPAR, sedangkan respons terapi dapat diprediksi dari kadar suPARdan PAI-1. Dibutuhkan studi lebih lanjut untuk validiasi model-model prediksi ini.Kata kunci: kanker paru karsinoma bukan sel kecil KPKBSK , miR-10b, miR-21, overall survival, plasminogen activator inhibitor 1 PAI-1 , respons terapi, soluble urokinase-type plasminogen activator receptor suPAR

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ABSTRACT
Lung cancer is associated with poor prognosis. Circulating markers to predict treatment response and prognosis is needed. Expression of microRNA10b miR 10b and fibrinolytic activity, as reflected by soluble urokinase type plasminogen activator receptor suPAR and the plasminogen activator inhibitor 1 PAI 1 , were promising as biomarker candidates.This study aimed to evaluate the role of miR 21, miR 10b expression, suPAR and PAI 1 levels as predictors of progression during treatment and treatment response in advanced lung cancer patients.This was cohort and survival study in Dharmais Cancer Hospital DCH . The subjects were non small cell lung cancer NSCLC patients diagnosed between March 2015 and September 2016. Expression of miRNAs were quantified using real time polymerase chain reaction RT PCR method. Levels of suPAR and PAI 1 were assayed using the enzyme linked immunosorbent assay ELISA method. Treatment response was evaluated based on RECIST 1.1. Patients were followed up until death or one year after treatment.Forty patients were enrolled 25 completed at least 4 cycles of chemotherapy and15 patients died during treatment. Absolute and FC miR 21 were not associated with progression or treatment response. Absolute MiR 10b expression 592,145 copies mL or FC miR 10b 0.066 were protective for progressive disease and poor treatment response, while suPAR levels 4,237 pg mL was a risk factor for progressive disease and poor responders. Since FC miR 10b was an important predictive factor, it was included in the prediction model of progression. PAI 1 levels 4.6 ng mL was a protective factor for poor response group of patients. suPAR level was an independent risk factors for progression and poor response, while PAI 1 level was an independent protective factor of poor response.Conclusion A model to predict progression can be developed using miR 10b expression and suPAR levels, while treatment response can be predicted by suPAR and PAI 1 levels. Further studies are needed to validate this model.Key words miR 10b, miR 21, non small cell lung cancer NSCLC , overall survival, plasminogen activator inhibitor 1 PAI 1 , soluble urokinase type plasminogen activator receptor suPAR , treatment response

Abstrak :

Peran Th17 dalam keganasan, khususnya karsinoma sel hati, masih menjadi perdebatan. Sel Th17, sel penghasil IL-17, dilaporkan berhubungan dengan efek protumor dan antitumor sekaligus. Di lain sisi, sel Th1 yang menyekresikan IFN-γ memiliki sifat antitumor. Kemoembolisasi transarterial / transarterial chemo-embolization (TACE) diketahui dapat menyebabkan nekrosis tumor, namun peran TACE dalam memengaruhi sel Th17, Th1, IL-17, IFN-γ, dan rasio neutrofil limfosit (RNL) masih belum diketahui. Penelitian ini bertujuan untuk menentukan perubahan Th17, Th1, IL-17, IFN-γ, dan nilai RNL pada pasien KSH yang menjalani TACE.

Penelitian ini dilakukan sepanjang Juni 2015–Januari 2019 di RSCM dan beberapa rumah sakit jejaring di Jakarta. Desain potong lintang digunakan untuk membandingkan respons imun pasien KSH dengan sirosis hati. Desain kohort prospektif diterapkan untuk menilai hubungan respons imun dengan keberhasilan TACE. Pengambilan darah dilakukan sebelum dan 30 hari setelah tindakan TACE pada pasien KSH dan satu kali pada pasien sirosis. Nilai Th17 dan Th1 dianalisis menggunakan teknik flowcytometry, sedangkan nilai IL-17 dan IFN-γ diukur dengan teknik enzyme-linked immunosorbent assay (ELISA). Nilai RNL dihitung dari pembagian kadar neutrofil dengan limfosit yang diperoleh dari pemeriksaan hitung jenis. Respons terhadap TACE dievaluasi berdasarkan kriteria mRECIST.

Sebanyak 40 pasien sirosis dan 41 pasien KSH berpartisipasi dalam penelitian ini. Sebanyak 12 pasien dan 29 pasien termasuk ke dalam kelompok respons dan nonrespons, secara berurutan. Penurunan kadar AFP dan ukuran tumor secara bermakna ditemukan pada kelompok respons. Pada kelompok ini, juga ditemukan peningkatan bermakna kadar Th1, Th17, dan sel T CD4+/IFN-γ+/IL-17+ setelah TACE. Nilai IL-17, IFN-γ, dan RNL tidak berhubungan dengan respons TACE. Di samping itu, didapatkan peningkatan bermakna kadar CD4+/IFN-γ+/IL-17- pada kelompok nonrespons.

Simpulan: Peningkatan kadar Th1 dan Th17 dalam darah perifer yang diiringi dengan peningkatan sel T CD4+/IFN-γ+/IL-17+ didapatkan pada pasien KSH yang berespons baik terhadap TACE.

 

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The role of Th17 cells in malignancy, especially hepatocellular carcinoma, remains controversial. Th17 cells, IL-17 producing cells, were reported to be associated with both protumor and antitumor effects. On the other hand, Th1 cells, IFN-γ producing cells, had antitumor properties. Transarterial chemoembolization (TACE) is known for its potency to cause tumor necrosis, but its impact on Th17, Th1, IL-17, IFN-γ, and neutrophil-to-lymphocyte ratio (NLR) is still unclear. This study aims to determine the changes in Th17, Th1, IL-17, IFN-γ, and NLR levels in HCC patients treated with TACE.

This study was conducted from June 2015 to January 2019 at Cipto Mangunkusumo National General Hospital dan several affiliated hospitals in Jakarta. A cross-sectional study design was used to compare the immune response between HCC and liver cirrhotic patients. A prospective cohort study design was applied to assess the relationship between immune response and tumor response to TACE. Plasma sampling was obtained from HCC and cirrhotic patients that fulfilled the inclusion and exclusion criteria. Blood samples were collected immediately before and 30 days after TACE. Th17 and Th1 levels were measured using flowcytometry technique, while IL-17 and IFN-γ levels were quantified by using enzyme-linked immunosorbent assay (ELISA). The value of NLR was calculated by dividing the neutrophil count by the lymphocyte count. Responses to TACE were evaluated based on mRECIST.

A total of 40 cirrhotic and 41 HCC patients participated in this study. As many as 12 and 29 patients were included in the response and nonresponse group, respectively. In the response group, there were significant reduction of AFP levels and tumor size, as well as significant increase of Th1, Th17 and CD4+/IFN-γ+/IL-17+ T cells levels after TACE. Furthermore, there was an increase of CD4+/IFN-γ+/IL-17- levels in the non-response group. The values of IL-17, IFN-γ, and NLR were not related to TACE response.

Conclusion: Patients with good response to TACE had increased levels of circulating Th1, Th17, and CD4+/IFN-γ+/IL-17+ T cells.

Abstrak :
Pada pasien hemodialisis (HD), banyak penelitian di negara maju membuktikan hubungan yang erat antara inflamasi, komplikasi kardiovaskular, malnutrisi, dan mortalitas yang tinggi. Inflamasi yang ditandai dengan meningkatnya IL-6 dan CRP, serta berkurangnya sitokin anti-inflamasi IL-10, mempunyai peran utama dalam terjadinya berbagai komplikasi pada pasien HD di Indonesia, terdapat perbedaan pelaksanaan HD, yaitu HD yang lebih jarang (2 kali seminggu), banyak menggunakan dialiser selulosal diasetat, proses ulang, low flux, dan tanpa air yang sangat murni, yang kesemuanya menyebabkan risiko respons inflamasi yang tinggi. Pada kenyataannya, prevalensi inflamasi dan nilai rata-rata CRP di Indonesia lebih rendah. Polimorfisme gen IL-6-174G>C dan gen IL-10-1082G>A telah dibuktikan mempengaruhi tingkat produksi IL-6 dan CRP. Perbedaan proporsi alel G, C pada IL-6-174, dan alel G, A pada IL-1082, berbagai bangsa dan ras, mungkin menjadi penyebab perbedaan di atas. Sindrom inflamasi malnutrisi (SIM) pada pasien HD berbeda dengan malnutrisi pada populasi. Pada SIM, faktor inflamasi, uremia dan katabolisme protein lebih berperan. Hal ini memerlukan cara penilaian status malnutrisi yang berbeda. Penelitian ini dilakukan untuk mendapatkan frekuensi polimorfisme gen IL-6-174 dan IL-10-1082, mengetahui faktor yang berperan dalam SIM, mengetahui perbedaan prevalensi inflamasi pada pasien dengan malnutrisi dan sebagai validitas penilaian SGA. Telah dilakukan penelitian pada pasien yang menjalani HD 2 kali seminggu, 5 jam per kali HD, tanpa komplikasi penyakit lainnya, dan semua memakai dialiser selulosa diasetat yang diproses ulang. Dari 64 pasien yang diperiksa, didapatkan gen IL-6-74GG 95,31%, CC 3,13% dan GC 1,56%. Gen IL-1082AA 89,06%, GA 10,94%, dan GG tidak didapatkan. Proporsi alel ini hampir sama seperti yang didapatkan di Korea, Jepang dan Cina, berbeda dengan yang didapat di AS, ras Kaukasia, Amerika-Afrika, Hispanik dan Eropa (Kaukasia). Selain perbedaan pada proporsi gen, kami mendapatkan konsenlrasi CRP (6,23±5,57 mg/L), frekuensi malnutrisi (24,7%), dan skor MIS (6,7) yang lebih rendah dibanding dengan data dari AS dan Eropa. Mengingat sedikitnya alel C pada gen IL-6-174 dan alel G pada gen IL-10-1082, analisis statistik yang dilakukan tidak dapat memperlihatkan pengaruh perbedaan alel terhadap manifestasi klinik. Inflarnasi kronik mempengaruhi terjadinya malnutrisi (PR 3,03; 1K 95% 1,53-6,06; P = 0,012). Penilaian dengan skala SGA berkorelasi balk dengan parameter antropometri (IMT, LLA, LOLA, HGS), dan albumin serum. Albumin serum sebagai parameter inflamasi kronik berkorelasi balk dengan parameter nutrisi yang lain, sedangkan CRP tidak. Didapatkan kesan yang kuat bahwa pada pasien HD, gen IL-174GG bersifat protektif, sedangkan gen IL-1082AA tidak begitu berperan. Selain itu dibuktikan adanya pengaruh inflamasi terhadap malnutrisi dan SGA terbukti merupakan penilaian sindrom malnutrisi inflamasi yang cukup baik.

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Many studies on HD patients in developed countries have conferred strong evidence of closed correlation between inflammation, cardiovascular complication and high mortality rates. Inflammation, indicated by high levels of CRP and IL-6, has a major role in initiating and sustaining complications. Adapting to high cost, HD in Indonesia is conducted in a little different ways. Patients are dialyzed twice a week, 5 hours each, using reprocessed cellulose/diacetate membrane dialyzer, and without ultrapure water. All of these contribute to a high risk of inflammation, but in fact the prevalence of inflammation in Indonesia is relatively low. IL-6-174G>C and IL-10-1082G>A polymorphic gene have been proven to influence the production of IL-6 and CRP. The difference in the proportion of allele G, C in IL-6-174, allele G, A in IL-1082 in a variety of people's races might cause the difference in the prevalence and the level of inflammation. Malnutrition inflammation syndrome (MIS) on HD patients is different from malnutrition in general population. In MIS, the inflammatory factors, uremia, and protein catabolism of protein are more dominant. These matters probably require a different assessment method of malnutrition status. The purpose of this study was to obtain the frequency of polymorphic gene IL-6-174 and IL-10-1082 to find out the prominent factors in MIS, and to find out the difference in the inflammation prevalence in patients with malnutrition and to serve as validity of SGA assessment. A study on patients who were on hemodialysis twice a week, 5 hours each session has been conducted. The subjects had no other co-morbidities and all of them used reprocessed diasetat cellulose dialyzers. Out of 64 patients examined, IL-6-174GG was obtained 95.31%, CC 3.13% and GC 1.56%, IL-1082AA 89.06%, GA 10.94%, but absence of GG genotype. The proportion of these alleles was almost similar to that obtained in Korea, Japan and China, but it was different from that obtained in the US for the Caucasian race, African Americans, Hispanic people, and the Caucasian people in Europe_ Besides the difference in gene proportion, it was obtained that CRP (6.23±5.57 mg/L), malnutrition (24.7%), and malnutrition inflammation score (6.7) were lower compared with the data from Europe and the United States. Considering the scanty amount of allele C in IL-6-174 gene and G allele in IL-10-1082 gene, based on the statistic analysis performed it did not revealed the influence of the difference in allele on the clinical manifestation. It was found that chronic inflammation influenced the occurrence of malnutrition (PR 3.03; CI 95% 1.53-6.06; P = 0,012). The scoring by the...

Abstrak :
ABSTRAK
Pasien kanker umumnya mengalami penurunan berat badan terkait kaheksia. Patofisiologi kaheksia kanker multifaktorial, termasuk efek sitokin pro inflamasi dan inflamasi sistemik. Profil asam amino plasma pada pasien kanker mengalami perubahan. Deplesi protein dapat terjadi akibat asupan yang menurun atau efek langsung dari tumor. Penelitian ini bertujuan untuk mengetahui profil dan hubungan antara asam amino serum, status nutrisi dan sitokin-sitokin pro-anti inflamasi, serta sel T helper 17 pada pasien kaheksia kanker paru. Penelitian potong lintang dengan consecutive sampling pada pasien kanker paru dengan kaheksia ini mengambil subjek berusia lebih dari 18 tahun dan belum diterapi atau sudah selesai terapi lebih dari 2 bulan di Rumah Sakit Kanker Dharmais. Analisis asupan dilakukan dengan food frequency questionnaire semikuantitatif dan 24-hours food recall. Pemeriksaan asam amino serum dengan metode spektofotometri, Sel T helper-17 dengan metode flowcytometry, dan C-reactive protein dengan metode latex agglutination, serta kadar IL 17, IL 6 dan TNFα dengan metode ELISA. Data yg didapat kemudian di analisis dengan uji T atau Mann Whitney untuk melihat hubungan dan untuk menganalisis hubungan dalam tabel digunakan uji Chi-Square atau Fischer Exact, sedangkan untuk korelasi digunakan uji Pearson atau Spearman. Asam amino triptofan, asparagin, glutamin, valin, lisin dan sistein berkorelasi positif dengan sitokin anti-inflamasi dan status nutrisi, sebaliknya negatif dengan sitokin pro inflamasi. Asam amino fenilalanin, treonin, dan glutamat berkorelasi positif dengan sitokin pro-inflamasi dan berkorelasi negatif dengan status nutrisi dan sitokin anti inflamasi. Khusus aspartat, selain berkorelasi positif dengan sitokin pro inflamasi, juga berkorelasi positif dengan indeks massa tubuh, tetapi menunjukkan korelasi negatif dengan penurunan berat badan. Beberapa asam amino serum terbukti berhubungan dengan status sitokin dan status nutrisi pada subjek kanker paru dengan kaheksia, sehingga perlu menjadi perhatian dalam terapi nutrisi pasien kanker Kata kunci: asam amino serum, status nutrisi, sitokin, kaheksia kanker

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ABSTRACT
Cancer patients generally experience weight loss associated with cancer cachexia. The pathophysiology of cancer cachexia is multifactorial, including the effects of pro inflammatory cytokines and systemic inflammation.. The plasma amino acid profile was found to significantly undergo changes in cancer patients. Protein depletion can occur due to decreased intake or direct effects of tumors on protein metabolism. This study aimed to determine the profile and relationship between serum amino acids, nutritional status and pro-anti-inflammatory cytokines, and T helper 17 cells in lung cancer cachexia patients. This cross-sectional study with consecutive sampling in lung cancer patients with cachexia took subjects over the age of 18 years and who had not been treated or who had finished therapy for more than 2 months at the Dharmais Cancer Hospital. Dietary intake analyses were carried out with semiquantitative food frequency questionnaire and 24-hour food recalls. Blood tests were carried out in the form of serum amino acids, cytokines, C-reactive protein and T helper 17 cells. Data obtained were then analyzed by the T or Mann Whitney test to see the relationship and to analyze relationships in the table used chi-square or Fischer Exact, while for correlation used Pearson or Spearman test. The amino acids tryptophan, asparagine, glutamine, valine, lysine and cysteine were positively correlated with anti-inflammatory cytokines and nutritional status, and negatively correlated with pro-inflammatory cytokines. Phenylalanine, threonine and glutamate amino acids were positively correlated with pro-inflammatory cytokines and negatively correlated with nutritional status and anti-inflammatory cytokines. Aspartate showed a positive correlation pro inflammatory cytokines and body mass index, but a negative correlation with weight loss. Some serum amino acids have been shown to be related to cytokines and nutritional status in lung cancer cachexia patients, so it should be a concern in nutritional therapy for cancer patients

Abstrak :
Fenomena utama pada pasien MDS adalah sitopenia di darah tepi, namun disertai kondisi hiperselular di sumsum tulang. sCD40L dianggap sebagai sitokin yang dapat memicu sintesis TNFα sebagai sitokin proapoptosis dan memicu sintesis VEGF sebagai sitokin proangiogenesis pada MDS. Oleh sebab itu sCD40L dianggap berpotensi sebagai biopenanda untuk memperkirakan perburukan pada MDS. Penelitian ini bertujuan untuk membuktikan peran pajanan rh-sCD40L dalam menginduksi sintesis TNFα dan VEGF pada sel progenitor hematopoesis, serta membuktikan peran pajanan TNFα dalam memicu apoptosis pada sel progenitor hematopoesis dan sel mesenkim MDS. Penelitian ini merupakan penelitian eksperimental in vitro komparatif. Subjek penelitian adalah pasien MDS yang didiagnosis dan diklasifikasikan berdasarkan kriteria WHO 2008. Pada bone marrow mononuclear cells (BMMC) dipajankan dengan rh-sCD40L dan antiCD40L, kemudian dilakukan pemeriksaan ekspresi mRNA TNFα dan mRNA VEGF yang dikuantifikasi dengan qRT-PCR, serta pemeriksaan kadar TNFα dan VEGF yang diperiksa dengan metode ELISA. Pada sel CD34+, CD33+, CD41+, dan CD73+ dipajankan rhTNFα kemudian dilakukan pemeriksaan aktivitas kaspase-3 dengan imunoflowsitometri. Terdapat 15 sampel MDS terdiri dari 4 dengan diagnosis RCUD, 7 RCMD, dan 4 RAEB1, serta 7 sampel kontrol. Pajanan rh-sCD40L meningkatkan ekspresi mRNA TNFα secara bermakna dibandingkan pajanan antiCD40L. Pajanan rh-sCD40L meningkatkan kadar TNFα secara bermakna dibandingkan kontrol. Namun pajanan rh-sCD40L tidak meningkatkan mRNA VEGF dan kadar protein VEGF. Pajanan rhTNFα meningkatkan aktivitas kaspase-3 pada sel progenitor MDS terutama yang berdiferensiasi menjadi mieloid (CD33+) dan megakariosit-trombosit (CD41+). Pajanan rhTNFα meningkatkan aktivitas kaspase-3 pada sel mesenkim (CD73+) MDS Simpulan: sCD40L berperan dalam meningkatkan sintesis sitokin proapoptosis TNFα di level mRNA dan protein, namun tidak terbukti berperan dalam meningkatkan sintesis proangiogenesis VEGF. TNFα berperan dalam meningkatkan apoptosis terutama pada sel hematopoesis yang telah berdiferensiasi menjadi seri mieloid dan seri megakariosit-trombosit, dan berperan dalam meningkatkan apoptosis pada sel mesenkim.

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Cytopenia is the primary phenomenon in Myelodysplastic Syndrome (MDS) patients, amidst hypercellular bone marrow. The soluble CD40 ligand (sCD40L) is considered as a cytokine that can trigger synthesis of TNFα and VEGF. The former is known as a cytokine that promotes apoptosis while the latter promotes angiogenesis in MDS patients. Therefore, the sCD40L may serve as a potential biomarker to predict worsening of MDS. This study aims to prove the role of rh-sCD40L exposure in inducing the synthesis of TNFα and VEGF in hematopoietic progenitor cells, as well as to establish the role of TNFα exposure in triggering apoptotic activity in hematopoietic progenitor and mesenchymal cells of MDS. The study was a comparative in vitro experimental study. Subjects were MDS patients diagnosed and classified using the WHO 2008 criteria. Bone marrow mononuclear cells (BMMC) were exposed to rh-sCD40L and antiCD40L. The expressions of TNFα and VEGF mRNAs were then quantified by qRT-PCR, and the level of TNFα and VEGF were measured using the ELISA method. The CD34+, CD33+, CD41+, and CD73+ cells were exposed to rhTNFα, then the activity of enzyme caspase-3 was measured using the immunoflowcytometry. There were 7 control and 15 MDS samples with the following diagnoses: 4 RCUD, 7 RCMD, and 4 RAEB1. Compared to antiCD40L, it is found that exposure of rh-sCD40L significantly increased the expression of TNFα mRNA. The similar exposure also significantly increased the level of TNFα compared to controls. However, the exposure of rh-sCD40L did not increase the expression of VEGF mRNA as well as the level of VEGF. The exposure of rhTNFα was found to increase the activity of caspase-3 in MDS progenitor cells, particularly those differentiated into myeloid cells (CD33+) and megakaryocyte-thrombocyte cells (CD41+). The exposure of rhTNFα was found to increase the activity of caspase-3 in MDS mesenchymal (CD73+) cells. Conclusion: The sCD40L plays a role in increasing the synthesis of TNFα which favors apoptotic activity in mRNA and protein level, but not in improving the synthesis of VEGF that promotes angiogenesis. Furthermore, TNFα plays a role in increasing apoptotic activity of hematopoietic cells, particularly those that have differentiated into myeloid series and megakaryocyte-thrombocyte series cells. Also TNFα plays a role in increasing apoptotic activity of mesenchymal cells.