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Abstrak :
Menarche dini merupakan salah satu faktor risiko kanker payudara yang berhubungan dengan lama pajanan estrogen. Penelitian mengenai faktor-faktor risiko menarche dini belum banyak dilakukan. Penelitian ini bertujuan untuk mengetahui hubungan antara asupan gizi, antropometri dan komposisi tubuh, serta aktivitas fisik dengan kadar estradiol dan menarche dini. Desain penelitian ini adalah potong lintang dengan subjek remaja putri 13-15 tahun di Jakarta, sejak Januari 2014 sampai Januari 2015. Analisis asupan gizi dilakukan dengan metode 24-hour recall dan Food Frequency Questionnaires (FFQ) semikuantitatif. Variabel antropometrik dan komposisi tubuh meliputi berat badan, tinggi badan, indeks massa tubuh (IMT), dan persentase lemak tubuh. Namun ditambahkan pengukuran lingkar lengan atas (LLA) dan lingkar pinggang (LP). Aktivitas fisik dinilai dengan Physical Activity Questionnaire (PAQ). Kadar estradiol serum diukur pada fase folikuler. Menarche dini adalah usia saat menstruasi pertama kali kurang dari 12 tahun. Terdapat 189 remaja putri usia13-15 tahun yang dilibatkan dari 8 SMP di Jakarta. Asupan gizi remaja putri berdasarkan PUGS cukup karbohidrat, kurang protein, tinggi lemak, dan rendah serat. Berdasarkan kriteria z-score IMT/U dari WHO, ditemukan sebanyak 3,2% gizi kurang, 73,5% normal, 18% mengalami overweight dan 5,3% mengalami obese. Lebih dari 90% subjek penelitian memiliki aktivitas fisik rendah. Proporsi menarche dini pada penelitian ini 22,8%. Kadar estradiol berkorelasi positif dengan asupan energi, protein, dan lemak. Berdasarkan kategori asupan, median estradiol berhubungan dengan asupan karbohidrat dan lemak. Terdapat korelasi negatif antara kadar estradiol dan LLA, LP serta z-score IMT/U. Terdapat hubungan antara menarche dini dan variabel-variabel antropometrik LLA dan LP serta z-score IMT/U. Tidak terdapat hubungan antara menarche dini, asupan gizi, aktivitas fisik, dan kadar estradiol. Faktor determinan kadar estradiol adalah asupan energi, protein, lemak dan zscore IMT/U, sedangkan faktor determinan menarche dini adalah LP. Dari hasil penelitian disimpulkan bahwa untuk menurunkan faktor risiko kanker payudara, perlu memperhatikan faktor-faktor yang terkait kadar estradiol dan menarch. ......Early menarche has been known as a risk factor of breast cancer because its association with the length of exposure time to estrogen. There are not much studies has been done on risk factors of early menarche. The aim of this study was to know the association among nutritional intake, anthropometry and body composition, physical activity, estradiol level and early menarche. This was a cross-sectional study involving adolescent girls aged 13-15 years in Jakarta, between January 2014 and January 2015. Interview on nutritional intakes were done by using the 24-hour recall and semiquantitative Food Frequency Questionnaires (FFQ). The anthropometric and body composition variables included body weight, body height, body mass index (BMI) and body fat percentage; however, additional variables were also measured, i.e. mid-upper arm circumference (MUAC) and waist circumference (WC). Physical activity was assessed by using the Physical Activity Questionnaires (PAQ). Serum estradiol levels was measured during follicular phase. Early menarche was defined if the first menstruation occurred before the age of 12 years. There were 189 adolescent girls enrolled in this study from 8 junior high schools in Jakarta. Based on guidelines of balanced nutrition, nutritiotional intake of adolescent girls were adequate carbohydrate intake, low protein intake, high fat intake, and low fiber intake. based on the WHO z-scores of BMI per age, there was 3,2% underweight, 73,5% normal, 18% overweight and 5,3% obese subjects. More than 90% of the study subjects had mild physical activity. The proportion of early menarche was 22.8%. Estradiol level was positive correlated with the intakes of energy, protein, and fat. Based on the diet intake category, median estradiol level was associate with the intakes of carbohydrate and fat. There was a negative correlation between estradiol level and MUAC, WC, and z-scores BMI per age. There was an association between early menarche and antrophometric measures (MUAC and WC) and z-scores BMI per age. No association was found between early menarche and nutritional intake, physical activity, or estradiol level. Determinant factors of estradiol level were the intakes of energy, protein, fat, and z-score BMI per age; while determinant factor of early menarche was waist circumference. To conclude, in order to reduce breast cancer risk, we should paid attention on factors associated with increased estradiol level and early menarche i.e. fat intake, physical acitivity and normal body weight.

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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

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Tamoksifen merupakan obat pilihan utama pengobatan kanker payudara pada wanita dengan reseptor estrogen positif ER , namun pada penggunaan jangka panjang selama 5-10 tahun berisiko menyebabkan secondary cancer berupa kanker endometrium. Penelitian ini bertujuan mendapatkan metode analisis yang sensitif, spesifik dan selektif yang mampu mengukur konsentrasi tamoksifen dan 4-hidroksitamoksifen di dalam plasma sebagai upaya memprediksi terjadinya secondary cancer dan mengetahui pengaruh pemberian fraksi aktif terhadap konsentrasi tamoksifen dan 4-hidroksitamoksifen menggunakan Kromatografi Cair Kinerja Ultra Tinggi-tandem Spektrometri Massa sesuai kriteria EMEA. Myrmecodia erinacea Becc. diekstraksi secara maserasi dengan etanol 80 untuk memperoleh ekstrak etanol 80 lalu difraksinasi dengan n-heksana, etil asetat dan butanol untuk mendapatkan fraksi aktif dan dilakukan identifikasi senyawa kimia. Dilakukan uji sitotoksik dan toksisitas akut terhadap fraksi aktif, lalu uji aktivitas kemopreventif menggunakan 30 tikus betina yang terbagi menjadi 6 kelompok perlakuan, yaitu diberikan tamoksifen 20 mg/kb bb KP , aqua destilata KKN , minyak jagung KN dan kelompok uji yang diberikan fraksi uji yang setara dengan kuersetin dosis 100, 200 dan 400 mg/kb bb. Tamoksifen 20 mg/kg bb diberikan pada seluruh kelompok kecuali KN dan KKN , setelah 30 menit diberikan fraksi uji pada kelompok perlakuan, selama 20 hari. Metode analisis yang dikembangkan sensitif, spesifik dan selektif pada LLOQ 2,0 ng/mL, rentang kurva kalibrasi 2,0-200,0 ng/mL,volume injek 1 L dengan waktu retensi tamoksifen, 4-hidroksitamoksifen dan propranolol HCl pada 1,59; 1,14; dan 1,09 menit. Fraksi aktif terpilih adalah etilasetat memiliki rendamen 45,86 dengan kadar total fenol dan flavonoid 0,34 dan 0,02 dan mengandung apigenin, kaemferol, kuersetin dan rutin dengan kadar kuersetin 5,75 . Fraksi aktif memiliki IC50 802,42 ppm dan LD50 > 5000 mg/kb bb sehingga aman digunakan. Semua dosis fraksi aktif dapat menurunkan konsentrasi tamoksifen dan 4-hidroksitamoksifen dalam plasma. Kromatografi Cair Kinerja Tinggi tandem Spektrometri Masa dapat mengukur konsentrasi tamoksifen dan 4-hidroksitamoksifen dalam plasma, penurunan itu diduga karena fraksi aktif yang diberikan menghambat proses metabolisme tamoksifen dengan demikian maka fraksi aktif berpotensi sebagai sebagai kemopreventif.

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ABSTRACT
Tamoxyfen is the first choice of drug treatment for breast cancer in women with estrogen receptor positive ER , however in the long term use of 5 10 years they are exposed to risk of secondary cancer in the form of endometrial cancer. A sensitive, specific and selective analysis method is required to measure the concentrations of tamoxyfen and 4 hydroksitamoxyfen in plasma as an attempt to predict the occurrence of secondary cancer and its effect after administration of active fraction against concentrations of tamoksifen and 4 hidroksitamoksifen using Liquid chromatography tandem mass spectrometry was developed in accordance with EMEA criteria. Myrmecodia erinacea Becc. was extracted in 80 ethanol by maceration to obtain 80 ethanol extracts and then fractination was perfomed with n heksan, ethyl acetate and butanol to obtain the active fraction afterward the chemical compounds were identified. Acute toxicity and cytotoxic test were performed against active fraction, then activity as chemoprevention of ant nest plant M. erinacea Becc. was performed on 30 female rats, divided into 6 treatments, which were given tamoxyfen 20 mg kb bb Positive control , aqua distillata Normal Control , and corn oil Negative Control . The test group was given a test fraction equivalent to 100, 200 and 400 mg kb bb doses of quercetin. Tamoxyfen 20 mg kg bw was administered in the whole group except negative control and normal control , then 30 minutes later the test fraction was given to the treatment group according to the dose, and was carried out for 20 days. Sensitive, specific and selective analysis method was developed on the calibration curve range 2.0 ndash 200.0 ng mL. The chosen active fraction was etilasetat with yield of 45.867 , which had the highest value of total phenol and its flavonoida of 0.34 and 0.02 thus containing apigenin, quercetin, kaemferol and rutine with levels of quercetin 5.75 . Active fraction containing IC50 was 802.84 ppm and LD50 5000 mg kg bw so it is safe to be used. All doses of the active fraction could lower concentrations of tamoxyfen and 4 hydroxytamoxifen in plasma. Liquid chromatography tandem Mass Spectrometry can measure concentrations of tamoxifen and 4 hydroxytamoxifen in plasma. The decline was allegedly because the active fraction inhibited metabolism of tamoxiifen, therefore active fraction had potential as as chemopreventive.

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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