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"ABSTRAKLatar belakang. Karsinoma medular sulit dibedakan secara histopatologik dan imunohistokimia dengan karsinoma invasif NST dengan gambaran medular derajat 3, karena beberapa gambaran yang tumpang tindih. Pembedaannya sangat penting terkait perbedaan tatalaksana dan prognosis. Karsinoma invasif NST dengan gambaran medular derajat 3 dianggap varian dari karsinoma invasif NST derajat 3, sehingga dapat mewakilinya. Karsinoma medular menunjukkan indeks apoptosis yang lebih tinggi dibandingkan karsinoma invasif NST derajat 3. Tujuan penelitian ini adalah mengetahui apakah indeks apoptosis dapat digunakan untuk mempertajam diagnosis karsinoma payudara medular secara obyektif menggunakan indeks apoptosis. Bahan dan Cara. Dilakukan penelitian retrospektif observasional analitik secara potong lintang terhadap 20 kasus karsinoma medular dan 20 kasus karsinoma invasif NST derajat 3. Dilakukan penilaian indeks apoptosis dengan metode TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick endlabeling); selanjutnya membandingkan nilai keduanya dan menghitung titik potongnya. Dari titik potong yang didapat, selanjutnya dibandingkan indeks apoptosisnya pada sediaan simulasi core biopsy dan sediaan mastektomi/eksisinya pada kedua kasus. Hasil. Indeks apoptosis (IA) pada karsinoma medular lebih tinggi secara bermakna dibandingkan karsinoma invasif NST derajat 3 ( p 0,001). Berdasarkan kurva ROC, kami mendapatkan titik potong yang optimal pada IA 1.25. Uji kappa terhadap keselarasan sediaan core biopsy dan eksisi/mastektomi mendapatkan hasil 0,3. Kesimpulan. IA dapat digunakan untuk mempertajam diagnosis karsinoma meduler payudara pada sediaan eksisi/mastektomi. Didapatkan titik potong IA: dinyatakan ´medular´ apabila lebih besar/ sama dengan 1,25. IA potensial dapat membantu pada sediaan core biopsy jika >1.25 pada gambaran histopatologik yang memenuhi sebagian kriteria karsinoma medular.

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ABSTRACTBackground. Difficulties are often faced to differentiate between medullary breast carcinoma and invasive carcinoma of no special type with medullary features grade 3, due to morphology and immunohistochemistry overlapping features. It is important to differentiate between them due to differences in the treatment and prognosis . Invasive carcinoma NST with medullary features grade 3 is considered a variant of invasive carcinoma NST grade 3 so it can represent it. Some study showed that apoptotic index in medullary breast carcinoma is higher than invasive carcinoma of no special type grade 3. The aim of this study is to investigate whether apoptotic index can be more definitive in diagnosing medullary breast carcinoma. Patients and methods. This is a retrospective-analytic cross-sectional study using 20 cases of medullary breast carcinoma and 20 cases of invasive carcinoma of no special type grade 3. Apoptotic cell were assessed by TUNEL and the apoptotic index (AI) was calculated. Results. AI in medullary breast carcinoma is significantly higher than invasive carcinoma of no special type grade 3 (p 0,001). The cut off point of AI between medullary carcinoma and invasive carcinoma NST grade 3 is 1.25. Kappa test was done to determine the concordance between core biopsy simulation AI with the related excision/mastectomy and the result is 0,3. Conclusion. The AI can be used to improve diagnostic accuracy of medullary breast carcinoma in excision/mastectomy. The cut off point of the apoptotic index between medullary carcinoma and invasive carcinoma NST grade 3 is 1.25. Only if AI >1.25 can potentially be used to support the diagnosis of medullary carcinoma in core biopsy in case showing some of the medullary carcinoma morphologic criteria."

"Adrenomedulin merupakan peptida dengan berbagai aktivitas biologi baik pada keadaan fisiologis maupun pada keganasan. Pada keganasan adrenomedulin berperan sebagai faktor stimulasi proliferasi, menghambat apoptosis, serta menginduksi angiogenesis. Ekspresi adrenomedulin terutama dipengaruhi oleh hipoksia sehingga adrenomedulin banyak ditemukan pada berbagai tumor solid. Tujuan penelitian ini adalah untuk menganalisis ekspresi Adrenomedulin jaringan karsinoma payudara invasif NST baik yang metastasis dan non-metastasis, serta dilihat hubungan adrenomedulin dengan jumlah mitosis dan apoptosis yang dilakukan dengan memeriksa ekspresi Caspase-3. Metode penelitian: pada 50 kasus karsinoma payudara invasif NST dengan 25 sampel non-metastasis (N0) dan 25 sampel sisanya adalah sampel metastasis (N1) dilakukan pemeriksaan ekspresi adrenomedulin dan Caspase-3 dengan pulasan imunohistokimia, serta jumlah mitosis dengan pulasan HE. Hasil : ada perbedaan bermakna ekspresi Adrenomedulin pada jaringan karsinoma payudara invasif NST metastasis dengan non-metastasis (p=0,002) dan terdapat korelasi (koefisien korelasi Spearman 0, 490) antara ekspresi adrenomedulin dengan metastasis, ada perbedaan bermakna ekspresi Caspase-3 pada jaringan karsinoma payudara invasif NST metastasis dengan non-metastasis (p=0,038) dan ada korelasi (koefisien korelasi Spearman 0, 327) antara ekspresi Caspase-3 dengan metastasis, namun tidak ada perbedaan bermakna jumlah mitosis pada jaringan karsinoma payudara invasif NST metastasis dengan non-metastasis (p=0,004) dan tidak ditemukan korelasi (koefisien korelasi Spearman 0,188) antara mitosis dengan metastasis, tidak ada perbedaan bermakna antara ekspresi adrenomedulin dengan ekspresi Caspase-3 (p=0,697) maupun dengan mitosis (p=0,711) pada jaringan karsinoma payudara invasif NST metastasis dengan non-metastasis.

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Adrenomedullin is a peptide hormone with many biological activities either in physiological conditions or malignancy. Adrenomedullin in malignancy acts as a factor in stimulating proliferation, inhibiting apoptosis, and induces angiogenesis. Its secretion is influenced by hypoxia condition and cytokine secretion. Adrenomedullin is found in variety of solid tumors. The purpose of this study was to analyze the expression of adrenomedullin in invasive carcinoma NST of the breast tissue both metastatic and non-metastatic, and its relations with mitosis count and apoptosis.

Methods: in 50 cases of invasive carcinoma NST of the breast with 25 samples of non-metastatic (N0) and 25 metastastic (N1) samples were examined for the expression of adrenomedullin and Caspase-3 that investigated by immunohistochemistry staining, and mitosis count by HE staining. Apoptosis was investigated by the expression of caspase-3.

Results: There is significance differences of Adrenomedullin expression in breast invasive cancer NST tissue with metastasis compare to non-metastasis (p = 0.002) and correlation between the expression of adrenomedullin with metastasis to regional lymph node (Spearman coefficient correlation 0.490), there is significance differences of Caspase-3 expression in breast invasive cancer NST tissue with metastasis compare to non-metastasis (p = 0.038) and there is correlation between the expression of Caspase-3 with metastasis to regional lymph node (Spearman coefficient correlation 0.327), but there isn‟t significance differences in mitosis count between metastasis and non-metastasis (p = 0.906), there is no correlation between the expression of adrenomedullin and the expression of Caspase-3 (Spearman coefficient correlation 0.089) and mitosis (Spearman coefficient correlation 0.099).

Conclusion: adrenomedullin expression are found correlate to metastasis to the lymph nodes in breast cancer invasive NST, but there were no correlation with mitosis and apoptosis."

"Latar Belakang : Kanker payudara adalah kanker kedua tersering pada wanita denganangka kcmatian yang tinggi. Keganasan, cherno-resistance, dan kegagaJan tempi untuk menyembuhkan kanker payudara disebabkan oleb adanya sel punca kanker payudara (BCSCs). BCSCs mengekspresikan multigen untuk kelangsungan hidup, kemampuan self-renewal, dan kemampuan bennetastasis. LingkWlgan hipoksia memicu sel tumor untuk mengekspresikan gen pro-survival dan beradaptasi secara metabolik terhadap stres, sehingga memlcu pertumbuhan sel kanker.Inhibitor of Apoptosis Prolein(lAP), mengatur supresi apoptosis, kontrol pembelahan sel, dan promosi angiogenesis.Ekspresi gen survivin sangat tinggi di sei tumor Wltuk kclangsungan hidup.perkembangan tumor dan keganasan. Survivin sangat papuler dijadikan sebagai gen target kanker. Mendalami peran SUrYivin dalam kondisi hipoksia akan menjanjikanmanfaat terapeutik yang lebih baik. Dalam percobaan ini, ekspresi survivin akan diamati di BCSCs yang dibiakkan dalam media bebas serum yang diberi perlakuan hipoksia 1%dengan periode berbeda.Mctode : Sel punca diekstrak dari kanker payudara, kemudian diberi perlakuan hipoksia. RNA kemudian diisolasi dan diukur dengan spectrophotometry Wltuk menentukan kadar kemumian sampeL Setelah itu, One-Step qRT-PCR dilakukan untuk mendapatkan hasH ekspresi relatif gen survivin. Produk peR tersebut kemudian diproses dengan electrophoresis uotuk memastikan gen yang telat diamplifikasi.HasH : Kadar ekspresi gen survivin rnengalami penurunan di sci pWlca kanker payudara selama proses hypoxia dengan interval yang berbeda.Kesimpulan : Sci punca kanker payudara yang diberi perlakuan hypoxia yang berbedamenunjukkan kadar ekspresi gen survi.vin yang rendah. Ada kemungkinan bahwa seItersebut telah berdiferensiasi dalam popuJasi sel puncak. Penelitian tambahan perlu dilaksanakan untuk memastikan aktivitas apoptosis di sel puncak kanker payudara dalam kondisi hypoxia."

"Sel kanker kanker payudara jenis TNBC memiliki kadar MnSOD yang tinggi. Ekspresi MnSOD yang tinggi pada sel kanker TNBC dapat menghasilkan sel dengan kapasitas proliferasi tinggi, apoptosis minimal, dan resistensi terapeutik. Keberadaan teknologi edit genom CRISPR/Cas9 yang menargetkan MnSOD diyakini dapat menurunkan ekspresi MnSOD sehingga mengurangi aktivitas proliferasi sel kanker BT-549 dan meningkatkan apoptosisnya. MnSOD diketahui mengandung polimorfisme yang meningkatkan risiko berkembangnya kanker. Oleh karena itu, sangat penting untuk menganalisis ekson 2 dari pengeditan genom gen MnSOD pada sel BT-549. Pada penelitian ini, memanfaatkan kultur sel BT-549 untuk diperbanyak dan dilakukan pemisahan DNA, RNA, dan protein dari sel kultur. Analisis western blot MnSOD, survivin, caspase 3, caspase 9, cleaved caspase 3, dan cleaved caspase 9. Selain itu, ekspresi relatif mRNA MnSOD dan survivin dihitung menggunakan teknik qRT-PCR. Selain itu dilakukan sekuensing DNA, pemodelan homologi protein, dan prediksi protein pengeditan genom. Analisa fenotip terdapat analisis proliferasi sel juga dilakukan untuk menentukan waktu penggandaan, serta studi siklus sel flowcytometric. Pengukuran flow cytometric dari apoptosis juga dilakukan untuk menguji pengaruh genome editing pada MnSOD. Hasil pada pengeditan genom yang difokuskan pada ekson 2 gen MnSOD dapat menurunkan ekspresi relatif mRNA MnSOD dan ekspresi protein MnSOD. Selain itu, adanya genome editing pada MnSOD juga mempengaruhi pola proliferasi klon KO 11.3 dan 11.4 yang lebih lambat jika dibandingkan dengan sel WT; hal ini sesuai dengan hasil analisis siklus sel, yang menunjukkan persentase fase G0/G1 yang tinggi dan persentase fase S, G2/M yang rendah pada klon KO 11.3 dan 11.4 jika dibandingkan dengan WT. Penghambatan ekspresi MnSOD juga dapat meningkatkan kemampuan apoptosis sel, yang ditunjukkan dengan tingginya proporsi sel yang mengalami apoptosis yang diukur dengan flow cytometry, serta peningkatan kadar protein inisiator dan efektor apoptosis. Kesimpulannya, KO gen MnSOD pada sel BT-549 mengurangi ekspresi protein MnSOD, sehingga menghambat pertumbuhan sel dan mendorong kematian sel BT-549.

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It is known that TNBC cancer cells have a high level of MnSOD. High MnSOD expression in TNBC cancer cells can result in cells with a high proliferation capacity, minimal apoptosis, and therapeutic resistance. It is believed that the existence of CRISPR/Cas9 genome editing technology that targets MnSOD can decrease MnSOD expression, hence reducing the proliferative activity of BT-549 cancer cells and increasing their apoptosis. MnSOD is known to include polymorphisms that increase the risk of developing cancer. Therefore, it is crucial to analyze exon 2 of the MnSOD gene genome editing in BT-549 cells. Methods: This work utilized BT-549 cell culture to proliferate cells and to separate DNA, RNA, and protein from the cultured cells. Western blot analysis of MnSOD, survivin, caspase 3, caspase 9, cleaved caspase 3, and cleaved caspase 9. Additionally, the relative expression of MnSOD and survivin mRNAs was calculated using the qRT-PCR technique. There was DNA sequencing, protein homology modeling, and genome editing protein prediction. In phenotypic analysis, cell proliferation analysis was also performed to determine doubling time, in addition to flowcytometric cell cycle study. Flow cytometric measurement of apoptosis was also performed to examine the effect of genome editing on MnSOD. Result: Genome editing focused at exon 2 of the MnSOD gene can reduce the relative expression of MnSOD mRNA and the expression of MnSOD protein. In addition, the existence of genome editing in MnSOD also affected the slower proliferation pattern of KO clones 11.3 and 11.4 when compared to WT cells; this is consistent with the results of cell cycle analysis, which demonstrated a high percentage of G0/G1 phase and a low percentage of S phase, G2/M, in KO clones 11.3 and 11.4 when compared to WT. The inhibition of MnSOD expression can also boost the capability of cell apoptosis, as indicated by the high proportion of cells undergoing apoptosis as measured by flow cytometry, as well as the elevated levels of apoptosis initiator and effector proteins. Conclusion: MnSOD gene knockout on BT-549 cells reduces MnSOD protein expression, hence inhibiting cell growth and promoting BT-549 cell death."

"[ABSTRAKTujuan: Menentukan hubungan ukuran tumor dan derajat histopatologi dengan metastasis tulang pada pasien kanker payudara berusia dibawah 40 tahun di RS Kanker Dharmais, membantu meningkatkan kualitas tatalaksana bagi klinisi.Metode: Analisa menggunakan data sekunder. Hasil ukuran tumor dikelompokkan menjadi ≤ 5 cm dan > 5 cm berdasarkan AJCC TNM staging system diperoleh melalui pencitraan radiologi payudara dari sistem PACS dan derajat histopatologi menurut derajat histopatologi Nottingham kombinasi diperoleh dari hasil ekspertise patologi anatomi, serta evaluasi metastasis tulang menggunakan skintigrafi tulang berdasarkan total populasi pasien kanker payudara berusia dibawah 40 tahun.Hasil: Jumlah subyek penelitian 32 perempuan kanker payudara berusia dibawah 40 tahun periode Januari 2011 hingga Juli 2014 di RS Kanker Dharmais. Tidak ada hubungan yang bermakna antara ukuran tumor dengan metastasis tulang (P= 0,715 (Fisher exact test), OR=1,71 (0,32-9,36)). Terdapat hubungan yang bermakna antara derajat histopatologi dengan metastasis tulang (P=0,010, P < 0,05).Dari 10 subyek derajat histopatologi tinggi, ternyata semua subyek mengalami metastasis tulang negatif. Pada subyek dengan derajat histopatologi sedang didapatkan 8 dari 15 subyek yang mengalami metastasis tulang. Pada subyek penelitian dengan derajat histopatologi rendah didapatkan 6 dari 7 subyek mengalami metastasis tulang negatif. Rerata usia 33,2 tahun dan simpang baku 3,7 tahun memiliki kejadian metastasis tulang lebih tinggi (P=0,024). Terdapat data tambahan dan ditemukan hubungan yang bermakna antara Cerb-b2/HER-2 positif dengan metastasis tulang (P=0,049 (P < 0,05), Odds Ratio=5,67 (0,84 ? 43,16)).Prevalensi metastasis tulang yaitu sebesar 28,1%.Kesimpulan: Pasien kanker payudara berusia dibawah 40 tahun dengan ukuran tumor besar tidak memiliki kejadian metastasis tulang lebih tinggi. Pasien dengan derajat histopatologi tinggi tidak memiliki kejadian metastasis tulang lebih tinggi, namun ditemukan angka kejadian metastasis tulang lebih tinggi pada derajat histopatologi sedang. Terdapat dua faktor lain yang juga mempunyai hubungan dengan kejadian metastasis tulang yaitu usia dan Cerb-br/HER-2. Rerata usia 33,2 tahun dengan simpang baku 3,7 tahun pada pasien kanker payudara berusia di bawah 40 tahun memiliki kejadian metastasis tulang lebih tinggi. Cerb-b2/HER-2 positif pada pasien kanker payudara berusia di bawah 40 tahun memiliki kejadian metastasis tulang lebih tinggi dengan resiko kejadian sebesar 5,67 kali. Prevalensi metastasis tulang cukup tinggi pada pasien kanker payudara berusia dibawah 40 tahun yaitu sebesar 28,1%.

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ABSTRACTObjective: Determine the relationship of tumor size and histopathology grade with bone metastases in breast cancer patients under 40 years old in Dharmais Cancer Hospital, to help improve the quality of management of the clinician.Methods: Analysis using secondary data. The results of tumor size are grouped into ≤ 5 cm and> 5 cm based on the AJCC TNM staging system from PACS system, obtained through breast radiology imaging and histopathologic grade according to histopathological Nottingham combination obtained from the anatomical pathology expertise, the evaluation of bone metastases using bone scintigraphy. These analyses are based on the total population of breast cancer patients under 40 years old.Results: The study subjects are 32 female breast cancer under 40 years old from January 2011 to July 2014 Dharmais Cancer Hospital. There is no significant relationship between the tumor size with bone metastasis (P = 0.715 (Fisher exact test), OR = 1.71 (0.32 to 9.36)). There is a significant relationship between the histopathology grade with bone metastases (P = 0.010, P <0.05). From 10 subjects with high grade histopathology, all subjects have no bone metastases. In subjects with moderate grade histopatholog, 8 of 15 subjects have bone metastases. In subjects with a low grade histopathology showed 6 of 7 subjects have no bone metastases. The mean age of 33.2 years and standard deviations of 3.7 years had a higher incidence of bone metastases (P = 0.024). There are additional data and found a significant association between Cerb-b2 / HER-2 positive patients with bone metastases (P = 0.049 (P <0.05), odds ratio = 5.67 (0.84 to 43.16)). The prevalence bone metastasis is equal to 28.1%.Conclusion: Breast cancer patients under 40 years with large tumor size did not have a higher incidence of bone metastases. Patients with a high grade histopathology do not have higher incidence of bone metastases, but found the incidence of bone metastases was higher in moderate grade histopathology. There are two other factors that also have a relationship with the incidence of bone metastases, that are age and Cerb-br / HER-2. The mean age of 33.2 years with standard deviations of 3.7 years in patients with breast cancer under 40 years old have a higher incidence of bone metastases. Cerb-b2 / HER-2 positive breast cancer patients under 40 years old have a higher incidence of bone metastases with the risk of occurrence 5.67 times. The prevalence of bone metastases in breast cancer patients under the age of 40 years is quite high equal to 28.1%.;Objective: Determine the relationship of tumor size and histopathology grade with bone metastases in breast cancer patients under 40 years old in Dharmais Cancer Hospital, to help improve the quality of management of the clinician.Methods: Analysis using secondary data. The results of tumor size are grouped into ≤ 5 cm and> 5 cm based on the AJCC TNM staging system from PACS system, obtained through breast radiology imaging and histopathologic grade according to histopathological Nottingham combination obtained from the anatomical pathology expertise, the evaluation of bone metastases using bone scintigraphy. These analyses are based on the total population of breast cancer patients under 40 years old.Results: The study subjects are 32 female breast cancer under 40 years old from January 2011 to July 2014 Dharmais Cancer Hospital. There is no significant relationship between the tumor size with bone metastasis (P = 0.715 (Fisher exact test), OR = 1.71 (0.32 to 9.36)). There is a significant relationship between the histopathology grade with bone metastases (P = 0.010, P <0.05). From 10 subjects with high grade histopathology, all subjects have no bone metastases. In subjects with moderate grade histopatholog, 8 of 15 subjects have bone metastases. In subjects with a low grade histopathology showed 6 of 7 subjects have no bone metastases. The mean age of 33.2 years and standard deviations of 3.7 years had a higher incidence of bone metastases (P = 0.024). There are additional data and found a significant association between Cerb-b2 / HER-2 positive patients with bone metastases (P = 0.049 (P <0.05), odds ratio = 5.67 (0.84 to 43.16)). The prevalence bone metastasis is equal to 28.1%.Conclusion: Breast cancer patients under 40 years with large tumor size did not have a higher incidence of bone metastases. Patients with a high grade histopathology do not have higher incidence of bone metastases, but found the incidence of bone metastases was higher in moderate grade histopathology. There are two other factors that also have a relationship with the incidence of bone metastases, that are age and Cerb-br / HER-2. The mean age of 33.2 years with standard deviations of 3.7 years in patients with breast cancer under 40 years old have a higher incidence of bone metastases. Cerb-b2 / HER-2 positive breast cancer patients under 40 years old have a higher incidence of bone metastases with the risk of occurrence 5.67 times. The prevalence of bone metastases in breast cancer patients under the age of 40 years is quite high equal to 28.1%.;Objective: Determine the relationship of tumor size and histopathology grade with bone metastases in breast cancer patients under 40 years old in Dharmais Cancer Hospital, to help improve the quality of management of the clinician.Methods: Analysis using secondary data. The results of tumor size are grouped into ≤ 5 cm and> 5 cm based on the AJCC TNM staging system from PACS system, obtained through breast radiology imaging and histopathologic grade according to histopathological Nottingham combination obtained from the anatomical pathology expertise, the evaluation of bone metastases using bone scintigraphy. These analyses are based on the total population of breast cancer patients under 40 years old.Results: The study subjects are 32 female breast cancer under 40 years old from January 2011 to July 2014 Dharmais Cancer Hospital. There is no significant relationship between the tumor size with bone metastasis (P = 0.715 (Fisher exact test), OR = 1.71 (0.32 to 9.36)). There is a significant relationship between the histopathology grade with bone metastases (P = 0.010, P <0.05). From 10 subjects with high grade histopathology, all subjects have no bone metastases. In subjects with moderate grade histopatholog, 8 of 15 subjects have bone metastases. In subjects with a low grade histopathology showed 6 of 7 subjects have no bone metastases. The mean age of 33.2 years and standard deviations of 3.7 years had a higher incidence of bone metastases (P = 0.024). There are additional data and found a significant association between Cerb-b2 / HER-2 positive patients with bone metastases (P = 0.049 (P <0.05), odds ratio = 5.67 (0.84 to 43.16)). The prevalence bone metastasis is equal to 28.1%.Conclusion: Breast cancer patients under 40 years with large tumor size did not have a higher incidence of bone metastases. Patients with a high grade histopathology do not have higher incidence of bone metastases, but found the incidence of bone metastases was higher in moderate grade histopathology. There are two other factors that also have a relationship with the incidence of bone metastases, that are age and Cerb-br / HER-2. The mean age of 33.2 years with standard deviations of 3.7 years in patients with breast cancer under 40 years old have a higher incidence of bone metastases. Cerb-b2 / HER-2 positive breast cancer patients under 40 years old have a higher incidence of bone metastases with the risk of occurrence 5.67 times. The prevalence of bone metastases in breast cancer patients under the age of 40 years is quite high equal to 28.1%., Objective: Determine the relationship of tumor size and histopathology grade with bone metastases in breast cancer patients under 40 years old in Dharmais Cancer Hospital, to help improve the quality of management of the clinician.Methods: Analysis using secondary data. The results of tumor size are grouped into ≤ 5 cm and> 5 cm based on the AJCC TNM staging system from PACS system, obtained through breast radiology imaging and histopathologic grade according to histopathological Nottingham combination obtained from the anatomical pathology expertise, the evaluation of bone metastases using bone scintigraphy. These analyses are based on the total population of breast cancer patients under 40 years old.Results: The study subjects are 32 female breast cancer under 40 years old from January 2011 to July 2014 Dharmais Cancer Hospital. There is no significant relationship between the tumor size with bone metastasis (P = 0.715 (Fisher exact test), OR = 1.71 (0.32 to 9.36)). There is a significant relationship between the histopathology grade with bone metastases (P = 0.010, P <0.05). From 10 subjects with high grade histopathology, all subjects have no bone metastases. In subjects with moderate grade histopatholog, 8 of 15 subjects have bone metastases. In subjects with a low grade histopathology showed 6 of 7 subjects have no bone metastases. The mean age of 33.2 years and standard deviations of 3.7 years had a higher incidence of bone metastases (P = 0.024). There are additional data and found a significant association between Cerb-b2 / HER-2 positive patients with bone metastases (P = 0.049 (P <0.05), odds ratio = 5.67 (0.84 to 43.16)). The prevalence bone metastasis is equal to 28.1%.Conclusion: Breast cancer patients under 40 years with large tumor size did not have a higher incidence of bone metastases. Patients with a high grade histopathology do not have higher incidence of bone metastases, but found the incidence of bone metastases was higher in moderate grade histopathology. There are two other factors that also have a relationship with the incidence of bone metastases, that are age and Cerb-br / HER-2. The mean age of 33.2 years with standard deviations of 3.7 years in patients with breast cancer under 40 years old have a higher incidence of bone metastases. Cerb-b2 / HER-2 positive breast cancer patients under 40 years old have a higher incidence of bone metastases with the risk of occurrence 5.67 times. The prevalence of bone metastases in breast cancer patients under the age of 40 years is quite high equal to 28.1%.]"

"ABSTRAKManifestasi klinis yang menonjol pada demam berdarah dengue adalah kebocoran plasma karena gangguan pada sel endotel vaskular. Anti NS-1 dapat bereaksi silang dengan Protein Disulfide Isomerase (PDI) pada sel endotel. Jambu biji biasa digunakan untuk mengatasi gejala dengue namun belum pernah ada penelitian secara in vitro untuk mengetahui mekanisme senyawa aktif yaitu lycopene yang terdapat di dalamnya. Tujuan penelitian ini adalah untuk mengetahui apakah lycopene dapat menurunkan apoptosis yang ditandai dengan Annexin V dan Heme oxygenase -1 (HO-1). Penelitian ini menggunakan kultur Human Umbillical Vein Endothelial Cells (HUVEC) yang diberi stimulasi anti NS-1 dan terdiri atas 5 perlakuan yaitu kontrol positif, kontrol negatif, dan lycopene dosis 0.5, 1 dan 2 μM. Kontrol positif adalah HUVEC yang diberi anti NS-1 dan basitrasin karena basitrasin sudah diketahui bekerja sebagai anti PDI dan dapat menghambat apoptosis. Kontrol negatif adalah kultur HUVEC yang diberi anti NS-1 tanpa perlakuan lycopene. Hasil penelitian menunjukkan bahwa hanya Annexin V pada kontrol positif menunjukkan hasil yang rendah secara bermakna dibandingkan perlakuan lainnya. Hal ini menunjukkan bahwa lycopene dengan dosis 0.5, 1 dan 2 μM tidak dapat menghambat apoptosis. Kadar HO-1 pada semua perlakuan tidak menunjukkan perbedaan bermakna. Hal ini menunjukkan bahwa baik basitrasin maupun lycopene tidak mempengaruhi metabolisme HO-1. Dapat disimpulkan bahwa senyawa lycopene dengan dosis dosis 0.5, 1 dan 2 μM tidak menunjukkan pengaruh dalam apoptosis sel endotel setelah terjadi infeksi dengue.

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ABSTRACTProminent clinical manifestation of dengue hemorrhagic fever is plasma leakage due to malfunction of endothelial cells. There is cross reaction between anti NS-1 and Protein Disulfide Isomerase (PDI) on endothelial cells. Psidium guajava is commonly used to improve condition in dengue symptoms but there is no research yet that study the in vitro mechanism how lycopene, a compound in Psidium guajava, works in this case. So this study aimed to know whether lycopene will decrease apoptosis of endothelial cells marked by Annexin V and Heme oxygenase-1 (HO-1) This study used Human umbillical vein endothelial cells (HUVEC) that given anti NS-1 stimulation and consisted of positive control, negative control and lycopene treatment with 0.5, 1 and 2 μM dose. Positive control is HUVEC with anti NS-1 and bacitracin that known act as anti PDI and inhibit apoptosis. Negative control is HUVEC with anti NS-1. Results showed that Annexin V only in positive control had lower Annexin V significantly compared to other treatments. This showed that lycopene 0.5,1 and 2 μM was not able to inhibit apoptosis. HO-1 in all treatments did not show significant difference. This showed that either bacitracin nor lycopene did not give effect to HO-1 metabolism. It was concluded that lycopene with 0.5, 1 dan 2 μM dose has no effect in endothelial cell apoptosis after dengue infection."

"Tujuan Studi ini adalah untuk mengetahui pengaruh hipoksia terhadap pola ekspresi gen HIF-1α pada jantung tikus serta mengamati timbulnya apoptosis pada kardiomiosit akibat hipoksia sistemik.Metode Hewan coba (tikus Sprague-Dawley) dibagi secara acak menjadi 7 kelompok (n= 4 per kelompok): kelompok kontrol normoksia (oksigen atmosfir), dan beberapa kelompok hipoksia yang ditempatkan dalam sungkup-hipoksik (kadar O2 8%) selama 1, 3, 7, 14, 21, dan 28 hari. Pemeriksaan ekspresi gen HIF-1α dilakukan dengan real-time PCR dan apoptosis dengan metode TUNEL.Hasil Dibandingkan dengan kelompok normoksia, ekspresi gen HIF-1α meningkat secara bertahap sejalan dengan lamanya hipoksia dan mencapai puncak pada hari ke-21. Tidak ada sel yang terlabel dengan cara TUNEL pada kelompok kontrol. Dibandingkan dengan kontrol, indeks apoptotik meningkat sejalan dengan lamanya hipoksia. Tidak ada hubungan bermakna antara peningkatan ekspresi HIF-1α dengan peningkatan indeks apoptotik.Kesimpulan Hipoksia sistemik kronik mengakibatkan peningkatan ekspresi mRNA HIF-1α dan apoptosis pada kardiomiosit.

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AbstractAim This study explored the expression of HIF-1α in hypoxic cardiac muscle in mice, and observed the evidence of apoptosis in hypoxia induced cardiomyocyte.Methods Male Sprague-Dawley rats, were randomized into 7 groups (n= 4 per group): control normoxia group that was exposed to atmospheric oxygen and hypoxia groups that were housed in hypoxic chambers (O2 level 8%) for 1, 3, 7, 14, 21, and 28 days respectively. Animals were sacrificed, hearts were rapidly excised, total RNA was extracted with an mRNA isolation kit and the expression of HIF-1α mRNA was then detected by real-time RT-PCR. Apoptosis was assessed by TUNEL method.Results For rat in hypoxia group, the expression of HIF-1α mRNA in cardiac myocytes was clearly up-regulated compared to the control normoxia group. Further, HIF-1α expression level elevated gradually and reached a peak at 21 days of hypoxia. No cell labeled by the TUNEL method was detected in the control group. Compared with the control group, the apoptotic index was significantly increased in the hypoxia group (P < 0.05). There was no significant correlation between the elevation of HIF-1α mRNA and the elevation of apoptotic index.Conclusion Systemic chronic hypoxia caused the elevation of HIF-1α mRNA and apoptosis in cardiac myocytes."

"Kanker serviks termasuk salah satu jenis kanker dengan tingkat prevalensi kasus yang tinggi di Indonesia. Berdasarkan GLOBOCAN 2020, ditemukan 36.633 (36% dari total kasus kanker pada wanita) kasus kanker serviks baru dan 21.003 kematian. Pengobatan terhadap kanker serviks saat ini masih menimbulkan efek samping seperti resistensi obat pada sejumlah kasus sehingga diperlukan alternatif pengobatan. Salah satu senyawa yang memiliki potensi antikanker, yaitu Eucalyptol. Eucalyptol adalah senyawa utama dalam tumbuhan eukaliptus seperti Eucalyptus globulus. Studi pengaruh konsentrasi eucalyptol terhadap viabilitas dan deteksi apoptosis sel HeLa dilakukan dengan konsentrasi 25, 50, 100 dan 200 μg/mL. Uji viabilitas dengan WST-1 menunjukkan bahwa variasi konsentrasi eucalyptol tersebut belum dapat menekan viabilitas sel HeLa (p>0,05 dengan uji ANOVA). Selanjutnya, deteksi apoptosis (menggunakan pewarna Annexin V-FITC) dengan mikroskop fluoresens menunjukkan bahwa variasi konsentrasi eucalyptol dapat menginduksi apoptosis dibandingkan nekrosis. Meskipun demikian, belum dilakukan pengamatan pada sel hidup sehingga tidak diketahui persentase sel apoptosis dan nekrosis dalam populasi total. Pengujian lanjutan dengan pewarna DAPI yang mewarnai sel hidup dan metode kuantifikasi lainnya untuk validasi hasil pengamatan dengan mikroskop fluoresens diperlukan.

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Cervical cancer is one type of cancer with a high case prevalence rate in Indonesia. Based on GLOBOCAN 2020, found 36,633 (36% of total cancer cases in women) new cervical cancer cases and 21,003 deaths. Treatment of cervical cancer is currently still causing side effects such as drug resistance in a number of cases so that alternative treatment is needed. One of the compounds that have anticancer potential is Eucalyptol. Eucalyptol is the main compound in eucalyptus plants such as Eucalyptus globulus. The study of the effect of eucalyptol concentration on the viability and detection of apoptosis of HeLa cells was carried out at concentrations of 25, 50, 100 and 200 g/mL. The viability test with WST-1 showed that the variation in eucalyptol concentration had not been able to suppress HeLa cell viability (p>0.05 by ANOVA test). Furthermore, detection of apoptosis (using Annexin V-FITC dye) by fluorescent microscopy showed that variations in eucalyptol concentration could induce apoptosis rather than necrosis. However, no observations have been made on living cells so that the percentage of apoptotic and necrotic cells in the total population is unknown. Further testing with DAPI dye that stains living cells and other quantification methods for validation of observations by fluorescent microscopy is required.

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"Apoptosis or programmed cell death is a normal condition for development and live multicellular organism. Apoptosis is a morphological phenomenon that play important role in physiological processes during fetal development and in adult. Mitochondria play an important role in apoptosis. Mitochondria can do apoptosis directly. Mitochondria has 2 family of protein Bcl-2. Bcl-2 and Bcl-XL are anti apoptosis while Bad and Bax are pro apoptosis. There are 3 different mechanism apoptosis. One generated by signals arising within the cell another triggered by death activators binding to receptors at the cell surface and a third may be triggered by dangerous agent that different from two ways before. Apoptosis also need caspase as cell death executor. Study of apoptosis still done especially in case of disease. Some disease have known related with disturbing of apoptosis mechanism for example cancer and auto immun. This article reviews about molecular mechanism of apoptosis for understanding disease and future therapy."

"A practical guide for the diagnostic surgical pathologist, this new edition of Biopsy Interpretation of the Breast presents the diverse spectrum of pathologic alterations that occur in the breast in a manner analogous to that in which they are encountered in daily practice. Lesions are grouped together according to their histologic patterns rather than by the traditional benign-malignant categorization in order to simulate the way pathologists face these lesions as they examine microscopic slides on a daily basis. The role of adjunctive studies in solving diagnostic problems in breast pathology is emphasized where appropriate.In addition, the clinical significance and impact on patient management of the various diagnoses are discussed and key clinical and management points highlighted."