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A Pilot Study on Immunohistochemical Expressions of NF-ĸB, Cyclin-D1, VEGF, and Cox-2 in Advanced Stage Laryngeal Carcinoma Pudji Rahaju; Ayunita Tri Wirattami; Ferry Sandra; Steffi Kurniawan; Khairun Nisa; Soehartono Soehartono; Edi Handoko; Ahmad Dian Wahyudiono; Hendradi Surjotomo; Hendy Setyo Yudhanto; Nanik Setjowati
The Indonesian Biomedical Journal Vol 13, No 4 (2021)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v13i4.1580

BACKGROUND: Progression of laryngeal carcinoma can be classified with the clinical staging, however there are different patterns of progressions observed in the patient with the same clinical stage which also affects their prognoses. Therefore biomarkers should be used. Nuclear factor (NF)-ĸB, Cyclin-D1, vascular endothelial growth factor (VEGF), cyclooxygenase (Cox)-2 have been reported for laryngeal carcinoma. However, it is still unclear how these markers are expressed and correlated in advanced stage laryngeal carcinoma. Therefore current study was conducted to investigate the expressions of NF-ĸB, Cyclin-D1, VEGF and Cox-2 and their correlations in advanced stage laryngeal carcinoma.METHODS: Subjects were recruited and laryngeal biopsies were collected, fixed in formalin and prepared for immunohistochemistry. The immunohistochemistry was performed using mouse monoclonal anti-NF-kB p65, anti-Cyclin-D12 anti-VEGF, and anti-Cox-2 antibodies. The immunohistochemistry results were documented and measured using ImmunoRatio. Pearson or Spearman correlation test was used based on the results of Shapiro-Wilk test of normality. A p-value of less than 0.05 is considered statistically significant.RESULTS: Twelve male subjects were included in this study. Expressions of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 were clearly observed. Mean of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 IHC expression levels measured with ImmunoRatio were 57.50±20.06%, 45.00±24.31%, 43.33±17.23% and 40.42±16.98%, respectively. There was significant correlation between the expressions of VEGF dan Cox-2 (p=0.031, r=0.622).CONCLUSION: Since correlation between the VEGF and Cox-2 expressions was statistically significant, VEGF and Cox-2 might have important roles in the growth, invasion and metastasis of laryngeal carcinoma.KEYWORDS: advanced stage laryngeal carcinoma, immunohistochemistry, NF-ĸB, Cyclin-D1, VEGF, Cox-2

Korelasi ekspresi IL-6 dengan STAT3 pada metastasis penderita KNF WHO tipe 3 LMP-1 positif S. Soehartono; Monika Teresa Prasetyo; Hendradi Surjotomo; Hendy Setyo Yudhanto
Oto Rhino Laryngologica Indonesiana Vol 49 (2019): Volume 49, No. 2 July - December 2019
Publisher : PERHATI-KL

Latar belakang: Karsinogenesis karsinoma nasofaring sangat kompleks, dan disebabkan oleh interaksi antara infeksi kronis Epstein-Barr Virus (EBV), faktor lingkungan, dan perubahan genetik serta epigenetik. Latent Membrane Protein (LMP)-1 merupakan antigen utama EBV. LMP-1 diyakini menstimulasi ekspresi sitokin yang memengaruhi perilaku sel epitel, salah satunya adalah Interleukin (IL)- 6. IL-6 akan mengaktivasi jalur Signal Transducer and Activator of Transcription (STAT)3. Peningkatan ekspresi IL-6 dan STAT3 memiliki kaitan erat dalam lingkungan mikro tumor KNF, namun peran IL-6 dan STAT3 dalam modulasi migrasi dan invasi sel KNF masih belum jelas diketahui. Tujuan: Mengetahui korelasi antara ekspresi IL-6 dan ekspresi STAT3 di jaringan nasofaring dengan metastasis penderita KNF WHO tipe III LMP-1 positif. Metode: Penelitian observasional analitik dengan pendekatan cross-sectional yang melibatkan 15 penderita KNF WHO tipe III LMP-1 positif. Pemeriksaan ekspresi LMP-1, IL-6, dan STAT3 menggunakan metode pewarnaan imunohistokimia, dan hasilnya dihitung dengan menggunakan software ImmunoRatio. Penentuan stadium klinis metastasis berdasarkan pemeriksaan klinis dan penunjang radiologis, kemudian dievaluasi nilai TNM menggunakan AJCC 2017. Hasil: Analisis statistik ekspresi IL-6 dan STAT3 menunjukkan korelasi yang signifikan (p=0,020) dengan koefisien korelasi r=0,592. Tidak terdapat perbedaan ekspresi IL-6 yang bermakna di antara penderita stadium III, IVa, dan IVb (p=0,116). Terdapat perbedaan ekspresi STAT3 yang signifikan di antara penderita dengan stadium III, IVa, dan IVb (p=0,038). Kesimpulan: Semakin tinggi ekspresi IL-6 maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif semakin meningkat. Semakin tinggi stadium klinis, maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif akan meningkat. Kata kunci: karsinoma nasofaring, Virus Epstein-Barr, LMP-1, IL-6, STAT3 ABSTRACT Background:Carcinogenesis of NPC is complex interactions among chronic EBV infection, environmental factors, genetic and epigenetic. LMP-1 is EBV’s antigen most expressed in NPC cases. LMP-1 is believed to stimulate expression of cytokines that affect the behavior of epithelial cells, i.e. Interleukin-6 (IL-6) which will activate the STAT3 pathway. Increased expression of IL-6 and STAT3 has a close relationship in tumor microenvironment of NPC patients, but the role of IL-6 and STAT3 themselves in modulation of migration and invasion of NPC cells are not yet fully understood. Purpose: To find out the correlation between IL-6 expression and STAT3 expression in the nasopharyngeal tissue of NPC patients with LMP-1 positive metastatic WHO type III. Method: Observational analytic study with cross-sectional approach involving 15 patients WHO type III LMP-1 positive NPC patients. Examination of LMP-1, IL-6, and STAT3 using immunohistochemical, and the results were calculated using ImmunoRatio. Clinical staging of metastases based on clinical examination and radiological imaging then synchronized with AJCC 2017. Result: Expressions of IL-6 and STAT3 showed significant correlation (p=0.020) with coefficient r=0.592. There were no differences in IL-6 expression among patients with stage III, IVa, and IVb (p=0.116). There were significant differences in STAT3 expression among patients with stage III, IVa, and IVb (p=0.038). Conclusion: There was a significant positive correlation between IL-6 and STAT3 in tissue from WHO type III LMP-1 positive NPC patients. The higher the clinical stage, the expression of STAT3 in the nasopharyngeal tissue of positive WHO type III LMP-1 NPC patients will increase.

One Year Survival of Wild-Type Adenocarcinoma Lung Cancer Patients Receiving Chemotherapy at dr. Saiful Anwar Hospital, Malang Ungky Agus Setyawan; Hendy Setyo Yudhanto; Aura Madarina
Respiratory Science Vol. 2 No. 3 (2022): Respiratory Science
Publisher : Indonesian Society of Respirology (ISR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.36497/respirsci.v2i3.47

Background: Lung cancer is one of the most common malignancies that leads to mortality. In Indonesia, lung cancer ranks first in men and third in women. The most common histological type of lung cancer is adenocarcinoma. Adenocarcinoma lung cancer is divided into 2 types, namely EGFR mutations and no mutations (wild-type). Chemotherapy is the treatment of choice for advanced wild-type adenocarcinoma lung cancer. This study aimed to assess the one-year survival of wild-type adenocarcinoma lung cancer patients receiving chemotherapy. Method: This study used a cross-sectional study design.Data were taken from the medical records of cancer patients at Dr. Saiful Anwar Hospital Malang in 2018-2019. Data were processed and analyzed by chi-square test. Results: Of the 54 subjects, 24 patients received carboplatin/ pemetrexed (44.4%), 15 patients received carboplatin/paclitaxel (27.8%), 9 patients received carboplatin/gemcitabine (16.7%), 2 patients received pemetrexed (3.7%), and 4 patients received gemcitabine (7.4%). The chemotherapy drug regimen had no correlation with one-year survival (P=0.899). Conclusion: There wasno significant difference between one-year survival andchemotherapy drug regimens. This study required a larger sample to minimize bias.

Correlation of LMP-1 Expression with BCL11B in Undifferentiated Type Nasopharyngeal Carcinoma Ihda Dian Kusuma; Diah Prabawati Retnani; Hendy Setyo Yudhanto; Harun Al Rasyid; Kenty Wantri Anita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 6 No. 15 (2022): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v6i15.679

Background: Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Asia and in Indonesia with a high incidence and mortality. The high mortality rate of patients with NPC is caused by recurrence and metastases early in the disease process, even though they have been given a combination of standard NPC therapy, namely radiotherapy and chemotherapy. Recurrences generally occur after the initial modalities of radiotherapy. Toxicity due to therapy given over a long time can also increase mortality. This study aims to determine the expression of BCL11B in undifferentiated NPC and its correlation with LMP-1 so that it can provide an overview of the nature of CSC in NPC, which is thought to cause recurrence and metastases and provide a poor prognosis in patients with NPC. Methods: This study was an analytical observational study using a cross-sectional approach using 30 samples from nasopharyngeal biopsy tissue diagnosed with undifferentiated NPC at the anatomical pathology installation of Dr. Saiful Anwar General Hospital, Malang, Indonesia, between 2018-2020. LMP-1 and BCL11B expression was examined using the immunohistochemical method. Data analysis was performed univariate and bivariate with the help of SPSS software. Results: Statistical analysis using the Spearman correlation test between LMP-1 and BCL11B expression in undifferentiated NPC biopsy tissue showed a significant correlation (p=0.004) with a correlation coefficient of r=-0.511. Conclusion: The higher the expression of LMP-1, the lower the expression of BCL11B in nasopharyngeal biopsies of patients with undifferentiated.

Correlation of LMP-1 Expression with BCL11B in Undifferentiated Type Nasopharyngeal Carcinoma Ihda Dian Kusuma; Diah Prabawati Retnani; Hendy Setyo Yudhanto; Harun Al Rasyid; Kenty Wantri Anita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 6 No. 15 (2022): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v6i15.679

Background: Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Asia and in Indonesia with a high incidence and mortality. The high mortality rate of patients with NPC is caused by recurrence and metastases early in the disease process, even though they have been given a combination of standard NPC therapy, namely radiotherapy and chemotherapy. Recurrences generally occur after the initial modalities of radiotherapy. Toxicity due to therapy given over a long time can also increase mortality. This study aims to determine the expression of BCL11B in undifferentiated NPC and its correlation with LMP-1 so that it can provide an overview of the nature of CSC in NPC, which is thought to cause recurrence and metastases and provide a poor prognosis in patients with NPC. Methods: This study was an analytical observational study using a cross-sectional approach using 30 samples from nasopharyngeal biopsy tissue diagnosed with undifferentiated NPC at the anatomical pathology installation of Dr. Saiful Anwar General Hospital, Malang, Indonesia, between 2018-2020. LMP-1 and BCL11B expression was examined using the immunohistochemical method. Data analysis was performed univariate and bivariate with the help of SPSS software. Results: Statistical analysis using the Spearman correlation test between LMP-1 and BCL11B expression in undifferentiated NPC biopsy tissue showed a significant correlation (p=0.004) with a correlation coefficient of r=-0.511. Conclusion: The higher the expression of LMP-1, the lower the expression of BCL11B in nasopharyngeal biopsies of patients with undifferentiated.

HUBUNGAN ANTARA EKSPRESI CYCLIN D1 DAN SMOOTH MUSCLE ACTIN DENGAN KARSINOMA SEL BASAL KELOMPOK RISIKO REKURENSI RENDAH DAN TINGGI Berlian Anggraeni Putri; Diah Prabawati Retnani; Hendy Setyo Yudhanto; Holipah; Rose Khasana Dewi; Hery Susilo
Majalah Kesehatan FKUB Vol. 9 No. 2 (2022): Majalah Kesehatan
Publisher : Faculty of Medicine Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/majalahkesehatan.2022.009.02.1

Kanker kulit yang tersering dikelompokkan menjadi kanker kulit melanositik dan nonmelanositik. Kanker kulit nonmelanositik menempati urutan kelima terbanyak dari seluruh jenis kanker di dunia dengan jenis yang paling sering adalah karsinoma sel basal. Secara histopatologis karsinoma sel basal dibagi menjadi dua kelompok, yaitu kelompok risiko rekurensi rendah dan tinggi. Sifat Karsinoma sel basal yang proliferatif dan invasif membutuhkan marker yang dapat memprediksi keduanya, di antaranya adalah cyclin D1 dan smooth muscle actin (SMA). Penelitian ini untuk membuktikan adanya hubungan antara ekspresi cyclin D1 dengan karsinoma sel basal kelompok risiko rendah dan tinggi. Desain penelitian adalah observasional analitik dengan metode cross-sectional, sampel penelitian karsinoma sel basal ditetapkan sebanyak 30 sampel, terdiri dari 15 sampel kelompok risiko rekurensi rendah dan 15 sampel kelompok risiko rekurensi tinggi. Ekspresi cyclin D1 dan SMA pada sediaan imunohistokimia dinilai secara semi kuantitatif pada masing-masing kelompok kemudian akan dilakukan uji chi-square. Hasil penelitian ini menunjukkan bahwa ekspresi cyclin D1 memiliki hubungan dengan karsinoma sel basal kelompok risiko rekurensi rendah dan tinggi (p = 0,008 < 0,05), namun tidak berhubungan dengan ekspresi SMA (p = 0,389 > 0,05). Ekspresi cyclin D1 pada karsinoma sel basal kelompok risiko rendah memiliki skor yang lebih rendah dibandingkan dengan kelompok risiko rekurensi tinggi. Sementara pada SMA tidak didapatkan perbedaan yang bermakna. Kesimpulan penelitian ini, ekspresi cyclin D1 memiliki hubungan dengan karsinoma sel basal kelompok risiko rekurensi rendah dan tinggi, sedangkan SMA tidak berhubungan.

CASE REPORT A 30-year-old Woman with Multiple-Sites Metastasis Lung Adenocarcinoma and Coronavirus-19 Disease (COVID-19) Yokanan Naftali; Jani Jane Rosihaningsih Sugiri; Suryanti Dwi Pratiwi; Hendy Setyo Yudhanto
Malang Respiratory Journal Vol. 4 No. 2 (2022): September 2022
Publisher : Universitaas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.mrj.2022.004.02.5

Background: Adenocarcinoma is the most common Non-Small Cell Lung Cancer (NSCLC) in non-smokers in Indonesia. It often metastasizes in multiple sites. Metastasis is a negative predictor for prognosis in lung adenocarcinoma. In this covid pandemic era we present a case of a 30-years-old woman with adenocarcinoma and multiple-sites metastasis, and Coronavirus-19 Disease (COVID-19). Case: A 30-year-old woman came to our hospital with multiple complaints of hearing loss, visual loss, and occasional shortness of breath. The patient had a history of wild-type EGFR adenocarcinoma and has been treated with 4 cycles of gemcitabine. She also presented with a lump in her neck. Further examination revealed multiple metastasis tumours in her brain, right eye, neck, and spine. Pleural fluid examination also showed a malignant pleural effusion. Nasopharyngeal swab using reverse transcriptase-polymerase chain reaction (rt-PCR) method revealed that she also suffers from COVID-19 with positive swab result. Despite adequate treatment, she rapidly deteriorates and passed away in hospital. Discussion: Management in this patient is complex due to multiple complications and limitation of management given in COVID-19 isolation ward. She presented with multiple equally complicated metastasis, in which treatment priority should be carefully assessed. Despite treatment by multiple specialists, her problems still persist and proved to be fatal. Conclusion: Although metastasis is common in adenocarcinoma, multiple metastasis is uncommon, and this case highlights the need of careful management priority in such patients in COVID-19 pandemic setting. Keywords: Adenocarcinoma, Multiple Metastasis, Lung Cancer, COVID-19

Tuberculous Dactilitis in Young Male, a Rare Case Adrian Yusdianto; Rezki Tantular; Yani Jane R. Sugiri; Teguh Rahayu Sartono; Dini Rachma Erawati; Hendy Setyo Yudhanto
Malang Respiratory Journal Vol. 5 No. 2 (2023): September Edition
Publisher : Universitaas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.mrj.2023.005.02.02

Introduction : Chylothorax is an uncommon medical condition caused by the accumulation of chylous fluid in the pleural space. Chylothorax has no predilection for sex or age. The prevalence after various cardiothoracic surgeries is 0.2% to 1%. Mortality and morbidity rates are around 10%. Respiratory distress may occur due to compression of the lung by the accumulated fluid. Management and approaches to treating the condition require multidisciplinary therapy, starting from non-pharmacological, pharmacological, to interventional management. Case Report : A 57-year-old Man patient was referred to the emergency room with chief complaint of shortness of breath. Reduced breathing sound on both lung fields. No previous history of cancer or thoracic surgery were found. X-ray examination had found bilateral pleural effusion. Thoracocentesis and pleural fluid analysis was performed with total of 6800 cc serosanguinous, whitish fluid was extracted from both of the lung. The patient was diagnosed with chylothorax. Lymphangiography and embolization was performed on the leak on left thoracic duct (T10) from right lymph node. Antibiotic was also given to treat the community acquired pneumonia that could be one of the possible etiology on this patient. Dietary modification with low fat diet and Ocreotide was also given to this patient as one of the treatment modalities. Discussion : The diagnosis of Chylothorax on this patient was established based on pleural fluid analysis and evidenced by lymphangiography examination by the presence of a leak in the thoracic lymphatic duct. Various modalities to diagnose this condition have been carried out with inconclusive results. Non-pharmacological, pharmacological and radiological interventions with embolization through lymphangiography are proven to be able to stop leaks and reduce symptoms in this patient. Conclusion : Chyle leak to the pleural space may compress the lung and cause respiratory distress. Combinaton of thoracocentesis, embolization of the leakage, dietary intake modification and administration of ocreotide may help prevent further chylous fluid accumulation.

Korelasi ekspresi IL-6 dengan STAT3 pada metastasis penderita KNF WHO tipe 3 LMP-1 positif S. Soehartono; Monika Teresa Prasetyo; Hendradi Surjotomo; Hendy Setyo Yudhanto
Oto Rhino Laryngologica Indonesiana Vol. 49 (2019): Volume 49, No. 2 July - December 2019
Publisher : PERHATI-KL

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32637/orli.v49i20.317

Latar belakang: Karsinogenesis karsinoma nasofaring sangat kompleks, dan disebabkan oleh interaksi antara infeksi kronis Epstein-Barr Virus (EBV), faktor lingkungan, dan perubahan genetik serta epigenetik. Latent Membrane Protein (LMP)-1 merupakan antigen utama EBV. LMP-1 diyakini menstimulasi ekspresi sitokin yang memengaruhi perilaku sel epitel, salah satunya adalah Interleukin (IL)- 6. IL-6 akan mengaktivasi jalur Signal Transducer and Activator of Transcription (STAT)3. Peningkatan ekspresi IL-6 dan STAT3 memiliki kaitan erat dalam lingkungan mikro tumor KNF, namun peran IL-6 dan STAT3 dalam modulasi migrasi dan invasi sel KNF masih belum jelas diketahui. Tujuan: Mengetahui korelasi antara ekspresi IL-6 dan ekspresi STAT3 di jaringan nasofaring dengan metastasis penderita KNF WHO tipe III LMP-1 positif. Metode: Penelitian observasional analitik dengan pendekatan cross-sectional yang melibatkan 15 penderita KNF WHO tipe III LMP-1 positif. Pemeriksaan ekspresi LMP-1, IL-6, dan STAT3 menggunakan metode pewarnaan imunohistokimia, dan hasilnya dihitung dengan menggunakan software ImmunoRatio. Penentuan stadium klinis metastasis berdasarkan pemeriksaan klinis dan penunjang radiologis, kemudian dievaluasi nilai TNM menggunakan AJCC 2017. Hasil: Analisis statistik ekspresi IL-6 dan STAT3 menunjukkan korelasi yang signifikan (p=0,020) dengan koefisien korelasi r=0,592. Tidak terdapat perbedaan ekspresi IL-6 yang bermakna di antara penderita stadium III, IVa, dan IVb (p=0,116). Terdapat perbedaan ekspresi STAT3 yang signifikan di antara penderita dengan stadium III, IVa, dan IVb (p=0,038). Kesimpulan: Semakin tinggi ekspresi IL-6 maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif semakin meningkat. Semakin tinggi stadium klinis, maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif akan meningkat. Kata kunci: karsinoma nasofaring, Virus Epstein-Barr, LMP-1, IL-6, STAT3 ABSTRACT Background:Carcinogenesis of NPC is complex interactions among chronic EBV infection, environmental factors, genetic and epigenetic. LMP-1 is EBV’s antigen most expressed in NPC cases. LMP-1 is believed to stimulate expression of cytokines that affect the behavior of epithelial cells, i.e. Interleukin-6 (IL-6) which will activate the STAT3 pathway. Increased expression of IL-6 and STAT3 has a close relationship in tumor microenvironment of NPC patients, but the role of IL-6 and STAT3 themselves in modulation of migration and invasion of NPC cells are not yet fully understood. Purpose: To find out the correlation between IL-6 expression and STAT3 expression in the nasopharyngeal tissue of NPC patients with LMP-1 positive metastatic WHO type III. Method: Observational analytic study with cross-sectional approach involving 15 patients WHO type III LMP-1 positive NPC patients. Examination of LMP-1, IL-6, and STAT3 using immunohistochemical, and the results were calculated using ImmunoRatio. Clinical staging of metastases based on clinical examination and radiological imaging then synchronized with AJCC 2017. Result: Expressions of IL-6 and STAT3 showed significant correlation (p=0.020) with coefficient r=0.592. There were no differences in IL-6 expression among patients with stage III, IVa, and IVb (p=0.116). There were significant differences in STAT3 expression among patients with stage III, IVa, and IVb (p=0.038). Conclusion: There was a significant positive correlation between IL-6 and STAT3 in tissue from WHO type III LMP-1 positive NPC patients. The higher the clinical stage, the expression of STAT3 in the nasopharyngeal tissue of positive WHO type III LMP-1 NPC patients will increase.

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