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"Latar belakang: Semaphorin-3B (SEMA3B) sebagai faktor antiangiogenik dan Cullin-1 (CUL1) sebagai faktor proangiogenik merupakan contoh dua protein yang bekerja secara antagonis dalam invasi trofoblas, yang bila terjadi ketidakseimbangan akan menyebabkan preeklamsia (PE). VEGF, MMP9, E-cadherin, p21, dan CASP3 merupakan kandidat protein terkait kaskade hantaran sinyal SEMA3B dan CUL1. Tujuan umum penelitian ini adalah untuk menganalisis kadar SEMA3B dan CUL1, serta kandidat protein terkait kaskade hantaran sinyalnya pada patologi PE berdasarkan perbedaan usia kehamilan saat persalinan. Metode: Penelitian diadakan di RS Cipto Mangunkusumo dan RS Budi Kemuliaan dari April 2017-April 2018. Studi potong lintang dengan observasi analitik dilakukan untuk mengukur kadar SEMA3B dan CUL1 dan kandidat protein terkait kaskade hantaran sinyalnya dalam plasenta, serta kadar SEMA3B dan CUL1 dalam serum ibu pada 70 pasien PE berdasarkan dua kelompok usia kehamilan saat persalinan: <34 minggu dan ≥34 minggu. Pemeriksaan dilakukan di Laboratorium Terpadu Fakultas Kedokteran Universitas Indonesia. Hasil: Kadar SEMA3B, CUL1, VEGF, dan E-cadherin secara bermakna lebih rendah pada kelompok usia kehamilan <34 minggu. Pada kelompok usia kehamilan <34 minggu: terdapat korelasi positif antara usia kehamilan dengan SEMA3B, CUL1, dan protein terkait kaskade hantaran sinyalnya; terdapat korelasi positif antara SEMA3B dengan VEGF dan p21; terdapat korelasi positif antara CUL1 dengan VEGF, MMP9, E-cadherin, p21, dan CASP3; dan korelasi negatif antara rasio p21/CUL1 dengan usia kehamilan. Pada kelompok usia kehamilan ≥34 minggu: terdapat korelasi positif antara SEMA3B dalam plasenta dengan SEMA3B dalam serum ibu; tidak ada korelasi SEMA3B dengan kandidat protein terkait kaskade hantaran sinyalnya; terdapat korelasi positif antara CUL1 dengan MMP9, E-cadherin, p21, dan CASP3. Kadar proangiogenik CUL1 dan VEGF yang rendah rendah dan ratio p21/CUL1 yang tinggi secara bermakna berhubungan dengan usia kehamilan <34 minggu saat persalinan. Analisis multivariat menunjukkan kadar CUL1 yang rendah meningkatkan risiko melahirkan sebesar empat kali lebih besar pada usia kehamilan <34 minggu dibandingkan usia kehamilan ≥34 minggu. Kesimpulan: Pada PE usia kehamilan <34 minggu saat persalinan, gambaran patologi PE lebih berat, kadar SEMA3B yang lebih rendah, serta kadar CUL1 yang lebih rendah memiliki risiko empat kali lebih besar terjadi persalinan dibandingkan usia kehamilan ≥34 minggu saat persalinan.

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Background: Semaphorin-3B (SEMA3B) as an antiangiogenic factor and Cullin-1 (CUL1) as a proangiogenic factor are examples of two proteins that work antagonistically in trophoblast invasion, which will cause preeclampsia (PE) if an imbalance occurs. VEGF, MMP9, E-cadherin, p21, and CASP3 are protein candidates related to the signal transduction cascade of SEMA3B and CUL1. The aim of this study was to analyze SEMA3B and CUL1 levels, as well as protein candidates related to the signal transduction cascade in pathology of PE based on differences in gestational age at delivery.

Methods: The study was conducted at Cipto Mangunkusumo Hospital and Budi Kemuliaan Hospital during April 2017 until April 2018. In this cross-sectional study SEMA3B, CUL1, and protein candidates related to the signal transduction cascade (VEGF, MMP9, E-cadherin, p21, CASP3) were measured in the placenta, as well as SEMA3B and CUL1 levels in maternal serum in 70 PE patients in two gestational age at delivery groups: <34 weeks and ≥34 weeks. Measurements were conducted at Integrated Laboratory of Faculty of Medicine Universitas Indonesia.

Results: Levels of SEMA3B, CUL1, VEGF, and E-cadherin were significantly lower in the gestational age group of <34 weeks compared to ≥34 weeks. In the gestational age group of <34 weeks: there were positive correlation between age gestational age and SEMA3B, CUL1, protein candidates related to their signal transduction cascade; there were positive correlations between SEMA3B and VEGF, p21; there were positive correlations between CUL1 and MMP9, E-cadherin, p21, CASP3; there were negative correlation between p21/CUL1 ratio and gestational age. In the gestational age group of ≥34 weeks: there were positive correlation between SEMA3B in placenta and SEMA3B in maternal serum; there were positive correlations between CUL1 and MMP9, Ecadherin, p21, CASP3; there were no correlation between SEMA3B and candidate protein related to the signal transduction cascade. Significantly, low level of proangiogenic CUL1 and VEGF, and high ratio p21/CUL1 were associated with <34 weeks of gestational age at delivery. Multivariate analysis showed that at <34 weeks of gestational age, low levels of CUL1 increased the risk of giving birth by four times greater than at ≥34 weeks of gestational age.

Conclusions: In PE at <34 weeks of gestation age at delivery, pathology of PE was worse, level of SEMA3B was lower, and lower level of CUL1 had four times greater risk of labor than at ≥34 weeks of gestational age at delivery. "

"[ABSTRAKLatar balakang. Sekitar 75% kanker leher rahim datang ke rumah sakit dalam stadium lanjut. Terapi utama kanker serviks stadium lanjut adalah radioterapi. Kombinasi terapi radiasi dengan kemoterapi ternyata tidak menghasilkan respons terapi yang lebih baik, tetapi bahkan menimbulkan efek samping yang lebih berat dibandingkan terapi radiasi saja. Perubahan pola makan saat ini, diduga berpengaruh pada respons terapi. Rasio asupan Polyunsaturated Fatty Acids (PUFA) n-6 : n-3 sekitar 1-2 : 1 dapat melawan pertumbuhan kanker. Beberapa publikasi melaporkan bahwa PUFA n-3 (AL n-3) mempunyai efek pro-apoptosis, anti-inflamasi, anti-proliferatif dan anti-angiogenik. Penelitian ini bertujuan untuk mengetahui apakah suplementasi nutrisi tinggi PUFA bersamaan dengan terapi radiasi dapat meningkatkan respons tumor pada kanker serviks stadium lanjut. Metode. Penelitian ini merupakan Randomized Clinical Trial, double blind pada pasien kanker serviks stadium lanjut, jenis karsinoma sel skuama yang hanya mendapat terapi radiasi di Departemen Radioterapi, Rumah Sakit Cipto Mangunkusumo (RSCM), Jakarta. Subjek penelitian diambil secara konsekutif, melalui randomisasi dibagi dua kelompok, yaitu kelompok perlakuan dan kontrol. Selama radiasi subjek penelitian mendapat suplementasi nutrisi mengandung isokalori dan isoprotein dengan rasio AL n-6 : n-3 = 1,27 : 1 dan kontrol. Selama perlakuan dilakukan evaluasi setiap lima kali radiasi, meliputi BB dan efek samping radiasi akut. Parameter yang dinilai adalah respons klinis, respons histopatologis serta perubahan kadar PGE2 dan VEGF serum.Hasil. Sebanyak 31 subjek dari 45 subjek dapat menyelesaikan penelitian. Sebelum perlakuan, status sosio-demografi, pola asupan AL n-6 dan n-3, status gizi dan klinis tidak didapatkan perbedaan bermakna. Setelah perlakuan, didapatkan penurunan kadar PGE2 serum pada kelompok perlakuan, sedangkan kelompok kontrol mengalami kenaikan (p = 0,127). Penurunan kadar VEGF kelompok perlakuan lebih besar dibanding kontrol (p = 0,626). Respons klinis dan respons histopatologis kelompok perlakuan lebih baik dibanding kontrol, dengan kemaknaan masing-masing p = 0,172 dan p = 0,169. Secara statistik belum didapatkan perbedaan yang bermakna pada penurunan kadar PGE2 dan VEGF serum, respons klinis dan respons histopatologis, tetapi didapat kemaknaan klinis yang nyata pada kelompok perlakuan dibanding kontrol. Analisis statistik gabungan dari respons klinis, respons histopatologis, kadar PGE2 dan VEGF serum didapatkan respons tumor total yang bermakna (p = 0,048).Kesimpulan. Suplementasi nutrisi tinggi PUFA dengan rasio asam lemak n-6 : n- 3 = 1,27 : 1 pada kanker serviks stadium lanjut bersama terapi radiasi memberikan respons tumor total yang lebih baik.;

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ABSTRACTBackground . Approximately 75% of uterine cervical cancer came to the hospital in an advanced stage. Primary therapy of advanced cervical cancer is radiotherapy. The combination of radiotherapy with chemotherapy did not give better outcomes, but even cause more severe side effects than radiotherapy. Changes in dietary intake at this time, are supposed to influence the response to therapy. The ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) about 1-2: 1 can fight cancer growth. Several publications stated that n-3 PUFA has pro- apoptotic effect, anti-inflammatory, anti-proliferative and anti-angiogenic. This study aimed to examine whether radiotherapy combined with daily nutritional supplements enriched PUFA enhance tumor response in advanced cervical cancer.Method. This study was a double-blind Randomized Clinical Trial (RCT) in patients with advanced squamous cell cervical cancer, received radiation only as control group, and those who received nutritional supplementation containing isocaloric and isoprotein with ratio of n-6 : n-3 PUFA = 1.27: 1 as treatment group. This study was performed in the Department of Radiotherapy Dr. Cipto Mangunkusumo General Hospital (RSUPNCM), Jakarta. Evaluation was done every five times radiation, including Karnofsky Perfomance Scale, body weight and side effects of acute radiation. Parameters assessed were clinical and hematological response, histopathological response and changes in the levels of PGE2 and VEGF serum,Results. A total of 31 subjects from 45 subjects participated the study completely. Prior to treatment, socio-demographic status, patterns of n-6 and n-3 PUFA, clinical and nutritional status were analyzed, no significant differences were noted. After treatment, a decrease in serum PGE2 levels in the treatment group was found, while in the control group increased (P = 0.127). VEGF in the treatment group declined higher than controls (P = 0.626). Treatment group showed significant better clinical response and histopathological responses compared to the control group (p = 0.172 and p = 0.169). No significant differences were found in the reduction of PGE2 and VEGF serum levels, clinical response and histopathological response, although from clinical standpoint there is a better significant response in the treatment group than the control. The combined statistical analysis of clinical response, histopathological response, PGE2 and VEGF serum levels obtained total tumor response (P = 0.048). Conclusion. Nutritional supplementation enriched PUFA (ratio of n-6: n-3 PUFA = 1.27 : 1) in advanced cervical cancer receiving radiotherapy gives better total tumor response.;Background . Approximately 75% of uterine cervical cancer came to the hospital in an advanced stage. Primary therapy of advanced cervical cancer is radiotherapy. The combination of radiotherapy with chemotherapy did not give better outcomes, but even cause more severe side effects than radiotherapy. Changes in dietary intake at this time, are supposed to influence the response to therapy. The ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) about 1-2: 1 can fight cancer growth. Several publications stated that n-3 PUFA has pro- apoptotic effect, anti-inflammatory, anti-proliferative and anti-angiogenic. This study aimed to examine whether radiotherapy combined with daily nutritional supplements enriched PUFA enhance tumor response in advanced cervical cancer.Method. This study was a double-blind Randomized Clinical Trial (RCT) in patients with advanced squamous cell cervical cancer, received radiation only as control group, and those who received nutritional supplementation containing isocaloric and isoprotein with ratio of n-6 : n-3 PUFA = 1.27: 1 as treatment group. This study was performed in the Department of Radiotherapy Dr. Cipto Mangunkusumo General Hospital (RSUPNCM), Jakarta. Evaluation was done every five times radiation, including Karnofsky Perfomance Scale, body weight and side effects of acute radiation. Parameters assessed were clinical and hematological response, histopathological response and changes in the levels of PGE2 and VEGF serum,Results. A total of 31 subjects from 45 subjects participated the study completely. Prior to treatment, socio-demographic status, patterns of n-6 and n-3 PUFA, clinical and nutritional status were analyzed, no significant differences were noted. After treatment, a decrease in serum PGE2 levels in the treatment group was found, while in the control group increased (P = 0.127). VEGF in the treatment group declined higher than controls (P = 0.626). Treatment group showed significant better clinical response and histopathological responses compared to the control group (p = 0.172 and p = 0.169). No significant differences were found in the reduction of PGE2 and VEGF serum levels, clinical response and histopathological response, although from clinical standpoint there is a better significant response in the treatment group than the control. The combined statistical analysis of clinical response, histopathological response, PGE2 and VEGF serum levels obtained total tumor response (P = 0.048). Conclusion. Nutritional supplementation enriched PUFA (ratio of n-6: n-3 PUFA = 1.27 : 1) in advanced cervical cancer receiving radiotherapy gives better total tumor response., Background . Approximately 75% of uterine cervical cancer came to the hospital in an advanced stage. Primary therapy of advanced cervical cancer is radiotherapy. The combination of radiotherapy with chemotherapy did not give better outcomes, but even cause more severe side effects than radiotherapy. Changes in dietary intake at this time, are supposed to influence the response to therapy. The ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) about 1-2: 1 can fight cancer growth. Several publications stated that n-3 PUFA has pro- apoptotic effect, anti-inflammatory, anti-proliferative and anti-angiogenic. This study aimed to examine whether radiotherapy combined with daily nutritional supplements enriched PUFA enhance tumor response in advanced cervical cancer.Method. This study was a double-blind Randomized Clinical Trial (RCT) in patients with advanced squamous cell cervical cancer, received radiation only as control group, and those who received nutritional supplementation containing isocaloric and isoprotein with ratio of n-6 : n-3 PUFA = 1.27: 1 as treatment group. This study was performed in the Department of Radiotherapy Dr. Cipto Mangunkusumo General Hospital (RSUPNCM), Jakarta. Evaluation was done every five times radiation, including Karnofsky Perfomance Scale, body weight and side effects of acute radiation. Parameters assessed were clinical and hematological response, histopathological response and changes in the levels of PGE2 and VEGF serum,Results. A total of 31 subjects from 45 subjects participated the study completely. Prior to treatment, socio-demographic status, patterns of n-6 and n-3 PUFA, clinical and nutritional status were analyzed, no significant differences were noted. After treatment, a decrease in serum PGE2 levels in the treatment group was found, while in the control group increased (P = 0.127). VEGF in the treatment group declined higher than controls (P = 0.626). Treatment group showed significant better clinical response and histopathological responses compared to the control group (p = 0.172 and p = 0.169). No significant differences were found in the reduction of PGE2 and VEGF serum levels, clinical response and histopathological response, although from clinical standpoint there is a better significant response in the treatment group than the control. The combined statistical analysis of clinical response, histopathological response, PGE2 and VEGF serum levels obtained total tumor response (P = 0.048). Conclusion. Nutritional supplementation enriched PUFA (ratio of n-6: n-3 PUFA = 1.27 : 1) in advanced cervical cancer receiving radiotherapy gives better total tumor response.]"

"ABSTRAKNama : LilisProgram Studi : Program Doktor Ilmu Biomedik Judul Disertasi : Peran Faktor Inflamasi Kronis dan Lingkungan Mikro Tumordi Stroma Peritumor dan Hubungannya dengan InvasiParametrium dan Metastasis KGB pada Karsinoma SelSkuamosa Serviks Stadium IB-IIA Pendahuluan: Salah satu penyebab tingginya angka kematian kanker serviksadalah kemampuan invasi dan metastasis sel kanker. Lesi di serviks sering disertaidengan inflamasi kronis dan peran inflamasi kronis dalam karsinogenesis telahdiketahui. Tujuan penelitian adalah mengeksplorasi faktor respons inflamasi danlingkungan mikro tumor LMT sebagai faktor prediksi invasi parametrium danmetastasis pada KGB pelvis.Metode: Terseleksi 75 kasus karsinoma sel skuamosa KSS serviks stadium IBIIAyang telah dihisterektomi dan limfadenektomi di RSUP Dr. CiptoMangunkusumo, Jakarta dan RSUP Dr. Hasan Sadikin RSHS , Bandung.Terdapat 15 kasus dengan invasi parametrium dan 18 kasus dengan metastasisKGB. Semua kasus dipulas H E dan imunohistokimia IHK yang dilakukan dilaboratorium PA-RSHS. Penanda untuk faktor inflamasi adalah CD4, CD8,CD68, IgG, dan penanda LMT adalah ?-SMA, TSP-1, CD31, VEGF-C. Semuapenanda dinilai pada stroma di 5 area LPB. Ekspresi IHK untuk sel inflamasikronis dihitung secara kuantitatif dan semikuantitatif untuk LMT. Hubunganantara reaksi inflamasi kronis dengan invasi parametrium dan metastasis KGBdianalisis dengan uji Mann-Whitney dan untuk faktor LMT dengan uji Chisquare.Hasil: Tiga variabel respons inflamasi kronis yaitu jumlah sel CD8 , CD68 ,IgG dan tiga faktor LMT yaitu imunoekspresi TSP-1, CD31, VEGF-C lebihrendah pada KSS serviks yang disertai invasi parametrium dibandingkan tanpainvasi parametrium. Terdapat hubungan jumlah sel CD8 p=0,015 dan VEGF-Cimunoekspresi yang rendah p=0,032 dengan kejadian invasi parametrium. Hasilanalisis ROC, didapatkan bahwa jumlah sel CD8 dengan titik potong

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ABSTRACTName LilisStudy Program Doctor in Biomedical ScienceTitle The role of chronic inflammation and tumormicroenvironment factors in parametrial invasion andpelvic lymph node metastasis in stage IB IIA of cervicalsquamous cell carcinoma Introduction One of the causes of the high mortality rate of cervical cancer is theability of cancer cells to invade and metastasis. Cervical lesions oftenaccompanied by chronic inflammation and the role of chronic inflammation incarcinogenesis is known. The objectives of this study is to explore inflammationresponse and tumor micro environment TME as predictors for parametrialinvasion PI and pelvic lymph node metastasis LNM .Methods Seventy five cases of cervical squamous cell carcinoma CSCC stageIB IIA which had underwent radical hysterectomy and lymphadenectomy at Dr.Cipto Mangunkusumo Hospital RSCM , Jakarta and Dr. Hasan Sadikin Hospital RSHS , Bandung were selected. There were 15 cases with PI and 18 cases withLNM. All slides were stained at pathological anatomy laboratory of RSHS, usingH E and immunohistochemistry IHC staining methods. Markers forinflammation factors are CD4, CD8, CD68, IgG and TME markers are SMA,TSP 1, CD31, VEGF C. All markers were evaluated in five fields of the stromaunder HPF magnification. The IHC expression of immune cells werequantitatively evaluated and semiquantitatively for TME. The association betweeninflammation response with PI and LNM were analyzed using non parametricalMann Whitney test and Chi square test for TME.Results Three variables of chronic inflammation response, CD8 , CD68 , IgG cell count and three TME expression variables, i.e., TSP 1, CD31 , VEGF C ,were lower in CSCC with parametrium invasion compared to in CSCC withoutparametrium invasion. A significant association between CD8 cell p 0,015 andVEGF C low expression p 0,032 with PI is identified. The ROC showed that acut off of CD8 cell count"

"ABSTRAKPasien kanker payudara di Indonesia sering mengalami ketidaknyamanan fisik dan psikologis, namun perawat belum dapat secara optimal membantunya. Hal ini terjadi antara lain karena sulitnya mengkaji kondisi/tingkat kenyamanan dan mengidentifikasi faktor-faktor yang mempengaruhi kenyamanannya. Penelitian ini bertujuan untuk mengembangkan instrumen pengkajian kenyamanan dan mengidentifikasi faktor-faktor yang mempengaruhi kenyamanan melalui suatu pemodelan teoritis kenyamanan dalam pendekatan Kolcaba. Penelitian ini diawali dengan studi literatur, wawancara mendalam dengan 10 pasien, dan konsultasikan dengan 10 orang pakar dari berbagai keilmuan terkait, dilanjutkan dengan menggunakan metode cross sectional untuk uji construct validity dan uji model teoritis dengan menggunakan Structural Equation Modelling pada 308 pasien kanker payudara. Hasil penelitian ini adalah instrumen pengkajian kenyamanan kanker payudara yang diberi nama ldquo;PKKP rdquo; dan pemodelan teoritis kenyamanan pada pasien kanker payudara di Indonesia dengan pendekatan Kolcaba. Hasil penelitian menjelaskan bahwa dukungan emosi, perawatan paliatif, spiritual, dan usia pasien mempengaruhi kenyamanan pasien melalui mediator kondisi fisik dan emosi. Pengembangan perawatan paliatif yang memperhatikan aspek psikologis, spiritual, dan karakteristik usia pasien, diperlukan di Indonesia untuk meningkatkan kenyamanan pada pasien kanker, khususnya pada pasien kanker payudara.

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ABSTRACTBreast cancer rsquo patients in Indonesia frequently experience physical and psychologist discomforts. Nevertheless, it is difficult for nurses, to precisely measure comforts and identify factors affecting comforts among cancer patients. This study aimed to develop a comfort assessment tool and generate a theoretical comfort model for breast cancer patients in Kolcaba approach. The first stage of this study used literature reviews, in depth interviews with 10 cancer patients, and consulted with 10 experts, followed by cross sectional method for construct validity test and theoretical model tests using Structural Equation Modelling to 308 breast cancer patients. Results of our study were the comfort assessment breast cancer instrument and a theoretical comfort model for breast cancer patients in Indonesia. The results of this research concluded emotional support, palliative care, spiritual, and patients rsquo age affects patients 39 comfort through the mediator of physical and emotional conditions. Our study suggested the development of palliative care that takes into account psychologist, spiritual and patient rsquo s characteristic aspect to promote comforts among breast cancer patients."

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Permasalahan pada kanker serviks meliputi permasalahan fisik, psikologis, sosial, spiritual dan seksual. Keperawatan holistik diperlukan dalam perawatan kanker serviks, spiritual merupakan dimensi inti yang akan mempengaruhi dimensi lainnya. Penelitian ini bertujuan untuk memperoleh model intervensi keperawatan spiritual dengan nilai-nilai Islami yang dinamakan model intervensi keperawatan spiritual Islami (INSPIRASI) dan mengetahui pengaruhnya terhadap kualitas hidup dan kesejahteraan spiritual perempuan kanker serviks. Penelitian ini terdiri dari tiga tahap. Tahap satu penelitian untuk mengidentifikasi masalah pada kanker serviks dengan desan mix method, pada studi kuantitatif dilakukan survey pada 93 responden, dan metode kualititaif dengan wawancara mendalam pada tujuh partisipan. Tahap dua pengembangan model dengan cara mengintegrasikan hasil studi tahap satu, studi literatur, dan konsultasi pakar. Tahap tiga dilakukan penelitian quasi eksperiment dengan desain pre-post test control group design. Metode sampling consecutive sampling pada perempuan kanker serviks stadium II-IV yang menjalani terapi kemoradiasi usia 25-68 tahun dengan jumlah sampel 80 (40 kelompok intervensi, 40 kelompok kontrol). Hasil penelitian teridentifikasinya permasalahan, gambaran kualitas hidup dan gambaran kondisi spiritual perempuan dengan kanker serviks, terbentuknya model intervensi keperawatan spiritual islami INSPRIRASI dan terujinya model intervensi. Hasil uji didapatkan terdapatnya pengaruh model INSPIRASI terhadap kualitas hidup (p=0.021) dan kesejahteraan spiritual  (p=0.001). Dengan demikian diharapkan model INSPIRASI dapat dijadikan salah satu strategi intervensi keperawatan pada perempuan dengan kanker serviks yang dapat meningkatkan kualitas hidup dan kesejahteraan spiritual.

 

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Problems in cervical cancer include physical, psychological, social, spiritual and sexual problems. Holistic nursing is needed in the treatment of cervical cancer, spiritual is a core dimension that will affect other dimensions. This study aims to obtain a model of spiritual nursing intervention with Islamic values called the Islamic spiritual nursing intervention model (INSPIRASI) and determine it is the effect on the quality of life and spiritual well-being of cervical cancer women. This research consisted of three stages. The first phase was to identify problems in cervical cancer with the desain mix method, a quantitative study surveyed 93 respondents, and a qualitative method with in-depth interviews with seven participants. The second phase of the model development was by integrating the results of the first phase study, literature study, and expert consultation. The third phase used a quasi-experimental study with a pre-posttest control group design. Method of consecutive sampling in women with stage II-IV cervical cancer undergoing chemo radiation therapy aged 25-68 years with total samples of 80 (40 intervention groups, 40 control groups). The results of the study identified problems, depictions of quality of life and depictions of the spiritual condition of women with cervical cancer, the formation of an Islamic spiritual nursing intervention model INSPIRASI and the testing of an intervention model. The test results found the influence of the INSPIRASI model on quality of life (p = 0.021) and spiritual well-being (p = 0.001). It is hoped that the INSPIRASI model can be used as one of the nursing intervention strategies in women with cervical cancer that can improve quality of life and spiritual well-being.

 

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"Kanker ovarium merupakan kanker paling mematikan ke-8 pada perempuan di dunia. Pasien kanker ovarium umumnya akan mengalami kemoresistensi, kekambuhan dan prognosis buruk setelah operasi sitoreduktif dan kemoterapi berbasis platinum. Hal tersebut berhubungan dengan peningkatan ekspresi Cancer Stem Cells (CSCs) CD44+/CD24-, RAD6, dan penurunan DDB2. Penelitian ini bertujuan untuk menganalisis hubungan ekspresi CSCs, RAD6 dan DDB2 dengan kemoresistensi kanker ovarium di jaringan kanker ovarium dan sirkulasi darah.Penelitian kohort ambispektif ini dilakukan di RSUP Cipto Mangunkusumo, RSUD Tarakan, RSUP Dharmais, dan RSUP Fatmawati pada Februari 2018–Februari 2022. Subjek adalah 64 orang pasien yang dibagi menjadi dua kelompok. Semua subjek menjalani operasi sitoreduktif dan pemeriksaan histopatologi. Kemoterapi diberikan sebanyak enam seri diikuti enam bulan observasi, kemudian ditentukan respons terapi dengan kriteria Response Criteria in Solid Tumors (RECIST). Uji imunohistokimia dilakukan langsung ke jaringan kanker ovarium (retrospektif) dan uji flowsitometri darah (prospektif) untuk menilai Ekspresi CSCs, RAD6 dan DDB2.Terdapat peningkatan Ekspresi CSCs, RAD6 serta penurunan bermakna ekspresi DDB2 (p < 0,05) di jaringan kanker ovarium kemoresisten, dan peningkatan bermakna Ekspresi CSCs, dan RAD6 yang bermakna (p < 0,05) di sirkulasi darah penderita kanker ovarium. Ekspresi DDB2 di uji imunohistokimia adalah protein dengan nilai AUC terbaik sedangkan di uji flowsitometri, CSCs memiliki nilai AUC terbaik. Disusun skor IHC-UNEDO (imunohistokimia) dan skor FCM- UNEDO (flowsitometri) untuk membantu memprediksi respons terapi.Penelitian ini menunjukkan bahwa terdapat peningkatan Ekspresi CSCs, RAD6 dan penurunan DDB2 di jaringan kanker ovarium, serta peningkatan Ekspresi CSCs di sirkulasi darah penderita kanker ovarium dan protein tersebut merupakan prediktor respons terapi kanker ovarium yang baik."

"ABSTRAKLatar Belakang: Persistensi infeksi HPV onkogenik merupakan penyebab kanker serviks. Retinol sebagai mikronutrien antioksidan memiliki peran esensial dalam sistem imun mencegah persistensi. Retinol memodulasi sel T CD4+/CD8+ serta produksi sitokin. Tumor Necrosis Factor-Alpha (TNF-) adalah sitokin pro-inflamasi yang mampu mengendalikan HPV, namun pada infeksi persisten TNF- justru memicu karsinogenesis. Rasio sel T CD4+:CD8+ dan TNF- yang adekuat di awal infeksi HPV merupakan titik kunci klirens. Penelitian ini bertujuan untuk mengetahui tingkat kecukupan deposit retinol, ekspresi TNF-, dan rasio sel T CD4+:CD8+ pada kelompok serviks normal, infeksi subklinis HPV klirens, persisten, dan kanker serviks.Metode: Tingkat kecukupan deposit retinol diketahui berdasarkan pemeriksaan darah perifer dengan metode ELISA. Stimulasi spesifik epitop E6 HPV tipe 16 dilakukan pada sel sekret servikovaginal yang telah diinkubasi 24 jam, diamati ekspresi TNF- secara semikuantitatif dengan metode ELISpot. Pemeriksaan sel T CD4+ dan CD8+ dari sekret servikovaginal secara kuantitatif dengan metode flowsitometri.Hasil: Deposit retinol yang cukup pada kelompok serviks normal, infeksi subklinis HPV klirens, persisten, dan kanker serviks berturut-turut adalah 85%, 75% (OR 1,89), 33,3% (OR 11,33), dan 75% (OR 1,89). Ekspresi TNF- pada kelompok serviks normal adalah 10%, sedangkan kanker serviks 75% (OR 27,00; p<0,001). Tidak tampak ekspresi TNF- pada kelompok infeksi subklinis HPV klirens dan persisten. Rasio sel T CD4+:CD8+ yang tinggi pada kelompok serviks normal adalah 10% dan kanker serviks 25% (OR 0,33). Tidak terdapat rasio sel T CD4+:CD8+ yang tinggi pada kelompok infeksi subklinis HPV klirens (OR 1,22) dan persisten (OR 0,95). Tidak terdapat hubungan bermakna antara tingkat kecukupan deposit retinol dengan ekspresi TNF- (p=0,147), tingkat kecukupan deposit retinol dengan rasio sel T CD4+:CD8+ (p=0,726), dan rasio sel T CD4+:CD8+ dengan ekspresi TNF- (p=0,690).Kesimpulan: Penelitian ini mampu membuktikan bahwa tingkat kecukupan deposit retinol tertinggi dijumpai pada kelompok serviks normal dan ekspresi TNF- tertinggi pada kelompok kanker serviks (OR 27,00; p<0,001). Tingkat kecukupan deposit retinol terendah bukan pada kelompok kanker serviks, melainkan pada infeksi subklinis HPV persisten (OR 11,33). Tidak terdapat perbedaan bermakna pada tingkat kecukupan deposit retinol dan rasio sel T CD4+:CD8+. Terdapat perbedaan bermakna pada ekspresi TNF- antara kelompok kanker serviks dengan serviks normal (p<0,001), kanker serviks dengan infeksi HPV subklinis klirens (p=0,024), dan klirens dengan persisten (p=0,007). Tidak terdapat perbedaan bermakna ekspresi TNF- antara kelompok kanker serviks dengan infeksi HPV subklinis persisten (p=0,058). Tidak bermaknanya beberapa hasil terkait imunitas masih mungkin dikarenakan tingkat kecukupan deposit retinol kelompok kanker serviks pada penelitian ini sangat baik dimana bertentangan dengan kepustakaan.

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ABSTRACT

Background: Persistency of oncogenic-HPV infection is the cause of cervical cancer. Retinol is one of antioxidant micronutrients that plays essential roles in immune system to prevent the persistency by modulating CD4+ and CD8+T cells and cytokines production. Tumor Necrosis Factor-Alpha (TNF-) is an acute pro-inflammatory cytokine which has many crucial roles in controlling HPV. In contrast, when persistent infection occurs, TNF- induces carcinogenesis. Ratio of CD4+:CD8+ T cells and adequate TNF- production in acute HPV infection are keypoints for clearance. The aim of this research is to analyze sufficency level of retinol deposit, expression of TNF-, and ratio of CD4+:CD8+ T cells in normal cervix, clearance and persistent HPV subclinical infection, and cervical cancer group.

Methods : Sufficiency level of retinol deposit was analyzed from peripheral blood by ELISA method. The cervicovaginal secretions which had 24 hours incubated were stimulated specifically by E6 epitope HPV type-16, measuring TNF- expression semiquantitatively by ELISpot method and CD4+/CD8+ T cells quantitatively by flowcytometry method.

Results: Sufficient level of retinol deposit in normal cervix, clearance HPV subclinical infection, persistent, and cervical cancer group was 85%, 75% (OR 1.89), 33.3% (OR 11.33), and 75% (OR 1.89), respectively. The expression of TNF- in normal cervix group was 10%, while in cervical cancer was 75% (OR 27.00; p<0.001). There were no expression in clearance and persistent HPV subclinical infection groups. High ratio of CD4+:CD8+ T cells in normal cervix and cervical cancer group was 10% and 25% (OR 0.33). There were no high ratio of CD4+:CD8+ T cells in clearance (OR 1,22) and persistent (OR 0.95) HPV subclinical infection groups. There was no significant correlation between sufficiency level of retinol deposit and TNF- expression (p=0.147), sufficiency level of retinol deposit and ratio of CD4+:CD8+ T cells (p=0.726), ratio of CD4+:CD8+ T cells and TNF- expression (p=0.690).

Conclusions: This study was able to prove that normal cervix group has the highest retinol deposit sufficiency level and cervical cancer group has the highest TNF- expression (OR 27,00; p<0,001). The lowest of retinol deposit sufficiency level was not in cervical cancer, but in persistent HPV subclinical infection group (OR 11.33). There was no significant correlation in sufficiency level of retinol deposit and ratio of CD4+:CD8+ T cells. There was significant correlation in TNF- expression between cervical cancer and normal cervix (p<0.001), cervical cancer and clearance subclinical HPV infection (p=0.024), and between clearance and persistent group (p=0.007). There was no significant correlation in TNF- expression between cervical cancer and persistent subclinical HPV infection group (p=0.058). Not significant some results related immunity that might be due to retinol deposit sufficiency level in cervical cancer group in this study was very good, which conflicted with literatures."

"Angka kematian kanker serviks masih tinggi karena banyak pasien datang berobat pada tahap lanjut. Respons terapi radiasi pada pasien kanker serviks stadium lanjut bervariasi walau dengan faktor klinikopatologi yang sama seperti stadium, massa tumor, jenis histopatologi, derajat diferensiasi, invasi limfovaskular, reaksi limfosit dan nekrosis. Oleh karena itu dipikirkan faktor prognosis lain seperti faktor apoptosis-survivin, telomerase dan sitokrom c. Penelitian ini bertujuan untuk mengetahui peran survivin, telomerase, dan sitokrom c sebagai prediktor respons terapi radiasi pada kanker serviks stadium lanjut khususnya stadium IIIB.Studi ini bersifat prospektif menggunakan metode nested case control. Pengambilan data dilakukan di Poliklinik Onkologi Departemen Obstetri dan Ginekologi RSCM serta Departemen Patologi Anatomi FKUI pada bulan Januari 2016 hingga Mei 2017. Pada subjek penelitian dilakukan wawancara, pemeriksaan histopatologi dan pemeriksaan biokimia secara ELISA untuk mengetahui kadar survivin, telomerase, sitokrom c, dan MRI pra-radiasi serta pasca-radiasi. Dari 90 subjek penelitian didapatkan rerata usia pasien 50 tahun, rerata massa tumor 6,7 cm dan sebagian besar berkeratin 84,4 , berdiferensiasi baik 81,1 , reaksi limfosit negatif 75,6 dan nekrosis 74,4 . Rerata faktor apoptosis-survivin, telomerase dan sitokrom c adalah 591,2 pg/mL, 5.223,2 pg/mL dan 191,3 ng/mL. Dari analisis bivariat didapatkan variabel yang berhubungan dengan respons terapi secara independen adalah massa tumor p = 0,1 , diferensiasi p = 0,17 , kadar survivin p = 0,01 , kadar telomerase p = 0,08 dan kadar sitokrom c p = 0,47. Hasil analisis multivariat didapatkan hubungan kadar survivin dan kadar telomerase dengan respons terapi radiasi p = 0,01 dan p = 0,07 . Tidak terdapat hubungan kadar sitokrom c dengan respons terapi radiasi p = 0,64 . Dengan model cox regresi survival didapatkan hazard ratio subjek dengan kadar survivin tinggi dan kadar telomerase tinggi terhadap respons terapi radiasi negatif adalah 4,20 dan 1,97.Simpulan: kadar survivin dan telomerase tinggi berhubungan dengan respons terapi radiasi negatif.

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Cervical cancer mortality rate is still high mostly due to patients seeking for help in advanced stage of the disease. Even with the same clinicopathologic features such as stage of the diseases, size of the tumor, histopathological types, level of differentiation, lymphocyte reaction and tumor necrosis, the radiotherapy outcomes still vary from patient to patient. Therefore, we thought another predictive factors like apoptosis inducing factors i.e. survivin, telomerase and cytochrome c as a new predictor of therapeutic resp onses on patients with stage IIIB squamous cell carcinoma of cervix.

This is a prospective study with nested case control method. Data collection was conducted in Oncology Polyclinic, Department of Obstetrics and Gynecology RSCM and Department of Pathological Anatomy of FKUI from January 2016 to May 2017. Subjects were interviewed, conducted histopathological and biochemical examination with ELISA to determine levels of survivin, telomerase, cytochrome c, and patients undergo pre and post radiation MR imaging.

There were 90 patients in this study with the mean of ages was 50 years, mean of tumor size was 6.7 cm and most subjects were keratinizing 84.4 , well differentiated 81.1 , negative lymphocyte reaction 75.6 and tumor necrosis 74.4 . The mean levels of apoptosis inducing factors survivin, telomerase and cytochrome c were 591.2 pg mL, 5,223.2 pg mL, and 191.3 ng mL.

Bivariate analysis showed the independent association between tumor size, level of differentiation, levels of survivin and telomerase p 0.1, p 0.17, p 0.01, p 0.08 . Multivariate analysis showed the correlation between levels of survivin and telomerase with radiation therapeutic response p 0.01 and p 0.07 and there was no association with level of cytochrome c p 0.64 With the survival cox regression models, the hazard ratio of subjects with high levels of survivin and telomerase on the negative radiation therapy responses were 4.20 and 1.97.Conclusion there were association between high levels of survivin and telomerase on the negative radiation therapy response. "

"ABSTRAKNama :Nugraha Utama PelupessyProgram Studi :S3 Ilmu KedokteranJudul :Marker Cancer Stem Cells CD133, CD44, dan ALDH1A1 Sebagai Faktor Prognostik pada Kanker Ovarium Tipe Epitelial Kanker ovarium merupakan penyakit yang bersifat heterogen dan kebanyakan pasien datang dengan stadium lanjut. Kanker ovarium epitelial tipe II mempunyai sifat pertumbuhan tumor yang cepat dan secara genetik labil dibandingkan tipe I. Keberadaan cancer stem cells CSC dianggap sebagai salah satu faktor prognostik terjadinya kemoresisten dan kesintasan hidup yang rendah.Penelitian ini bertujuan untuk membuktikan CSC sebagai faktor prognostik dengan menggunakan marker CD133, CD44, dan ALDH1A1 pada kanker ovarium tipe epitelial.Marker CD133, CD44, dan ALDH1A1 diperiksa dengan imunohistokimia dan flowcytometry. Hasil ekspresi marker CSC pasien kanker ovarium tipe I dan tipe II dimasukkan kedalam suatu tabel yang dihubungkan dengan respons kemoterapi dan kesintasan hidup. Analisis data dilakukan dengan program computer STATA 14. Analisis kesintasan dilakukan dengan analisis Kaplan-Meier dan uji asumsi cox proportional hazard. Analisis multivariat dipakai untuk model prognosis selama 10 bulan. Sistem skoring dibuat dengan menggunakan receiver operating characteristic ROC curve analyses.Data demografi kelompok terbanyak adalah usia ge; 45 tahun; 40 sampel 72,7 , stadium I, 23 sampel 41,8 , diferensiasi buruk 30 sampel 54,5 , dan tipe II 16 sampel 29,1 . Perbedaan yang bermakna antara tipe histopatologi dengan marker CSC hanya terlihat pada marker CD44. Skor Prediksi Kemoresisten SPKr 10 bulan yang dihubungkan dengan 4 variabel yaitu usia ge; 45 tahun, tipe II, stadium III minus;IV, dan CD44 tinggi dengan ROC 72,47 dan probabilitas post test 82,5 . Kurva ROC berdasarkan kombinasi marker CSC dan faktor klinikopatologi yaitu stadium III minus;IV, usia ge; 45 tahun, diferensiasi buruk, tipe II, CD133 negatif, CD44 tinggi, dan ALDH1A1 tinggi adalah 0,841. Skor Prediksi Kematian SPKm 10 bulan yang dihubungkan dengan 3 variabel yaitu stadium III minus;IV, tipe II, dan CD44 tinggi dengan AUC 80,44 dan probabilitas post test 78,7 . Kurva ROC berdasarkan kombinasi marker CSC dan faktor klinikopatologi yaitu stadium III minus;IV, usia ge; 45 tahun, diferensiasi buruk, tipe II, CD133 positif, CD44 tinggi, dan ALDH1A1 tinggi adalah 0,841.Simpulan: Marker CD44 terbukti berperan pada kanker ovarium tipe II. Skor Prediksi Kemoresisten dan Skor Prediksi Kematian dapat ditentukan selain dengan faktor klinikopatologi, juga dengan memakai marker CSC. Kata kunci: ALDH1A1, CD44, CD133, CSC, kanker ovarium epitelial, kesintasan hidup, respons kemoterapi.

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ABSTRACTName : Nugraha Utama PelupessyStudy Program : Doctoral Program Medical SciencesTitle :Cancer Stem Cell CD133, CD44 andALDH1A1 Markers As Prognostic Factors on Epithelial Ovarian Cancer. Ovarian cancer is a heterogeneous disease and most of the patients came with an advanced stage. Epithelial ovarian cancer type II has the characteristic of rapid tumor growth and genetically more labile than that of type I. The presence of cancer stem cells CSC is considered as one of the prognostic factors of low mortality and survival.The aims of this study was to prove CSC as prognostic factors using CD133, CD44, and ALDH1A1 markers on epithelial ovarian cancer.Clinicopathology and demographic data were collected from medical records. CD133, CD44, and ALDH1A1 markers were examined with flowcytometry and immunohistochemistry. CSC marker expression of the patients with ovarian cancer type I and II was connected with chemotherapy and survival response. Data analysis was done by using STATA 14 software. Survival analysis was done by using Kaplan-Meier analysis and Cox proportional hazard test. Multivariate analysis is used for prognosis model for ten months. Receiver Operating Characteristic ROC curve analyses was used as the system scoring. The highest group demographic data were age ge; 45 years; 40 samples 72.7 , stage I, 23 samples 41.8 , poor differentiation 30 samples 54.5 , and type II 16 samples 29.1 . A significant difference between the histopathologic type and the CSC marker was seen only in CD44 marker. Chemoresistance Prediction Score in 10 months was associated with 4 variables ie age ge; 45 years, type II, stage III minus;IV, and CD44 high with ROC 72.47 and posttest probability 82.5 . The highest chemoresitency scoring ROC curve based on the combination of CSC marker and clinicopathology factors; stage III minus;IV, age ge; 45 years, poor differentiation, type II, negative CD133, high CD44, and high ALDH1A1, was 0.841. Mortality Prediction Score in 10 months was associated with 3 variables is stage III minus;IV, type II, and CD44 high with AUC 80.44 and posttest probability 78.7 . The highest mortality scoring ROC curve based on the combination of CSC marker and clinicopathology factors; stage III minus;IV, age ge; 45 years, poor differentiation, type II, positive CD133, high CD44, and high ALDH1A1, was 0.841. Conclusion: The CD44 marker has a role in type II ovarian epithelial cancer. Chemoresistance Prediction Score and Mortality Prediction Score can be determined from clinicopathological factors and using CSC marker. Keywords: ALDH1A1, CD44, CD133, chemotherapy response, CSC, Epithelial Ovarian Cancer, survival"