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"Latar Belakang: Tipe terbanyak dari limfoma non-Hodgkin (LNH) sel B adalah Diffuse Large B-cell Lymphoma (DLBCL) yang merupakan entitas heterogen. Hans membagi DLBCL menjadi subtipe Germinal Center B-cell like (GCB) dan non-Germinal Center B-cell like (non-GCB) dengan tehnik pemeriksaan imunohistokimia menggunakan CD10, BCL6 dan MUM1. Caspase-3 adalah protein yang berperan utama dalam mekanisme apoptosis dan dapat mengalami mutasi somatik pada LNH. Imunoekspresi Caspase-3 dapat berhubungan dengan kesintasan pasien DLBCL. Tujuan penelitian ini untuk mengetahui perbedaan imunoekspresi Caspase-3 pada DLBCL subtipe GCB dan non-GCB. Bahan dan Metode: Pemeriksaaan imunoekspresi Caspase-3 pada 41 kasus DLBCL yang terdiri atas 18 kasus subtipe GCB dan 23 kasus non-GCB dilakukan dengan tehnik imunohistokimia . Subjek penelitian berasal dari RSCM dan enam rumah sakit lainnya di Jakarta. Hasil: Kasus DLBCL subtipe GCB memberikan hasil positif pada pulasan Caspase-3 berjumlah 13 kasus (72%) dan negatif berjumlah 5 kasus (28%). Hasil yang didapatkan dari subtipe non-GCB yaitu positif berjumlah 5 kasus (22%) dan negatif berjumlah 18 kasus (78%). Terdapat perbedaan bermakna imunoekspresi Caspase-3 antara DLBCL subtipe GCB dengan subtipe non-GCB (p = 0,002). Kesimpulan: Imunoekspresi Caspase-3 menunjukkan positivitas yang lebih tinggi pada DLBCL subtipe GCB dibandingkan dengan subtipe non-GCB.

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Background: The most common type of B-cell non-Hodgkin lymphoma (NHL) is diffuse large B-cell lymphoma (DLBCL) which is heterogeneous. Hans divided DLBCL into Germinal Center B-cell-like (GCB) and non-Germinal Center B-cell-like (non-GCB) subtypes by using immunohistochemistry staining with CD10, BCL6 and MUM1. Caspase-3 is a protein that functions as a key role in the mechanism of apoptosis and may have somatic mutation in NHL. Immunoexpression of Caspase-3 could be associated with the survival of DLBCL patient. This study was performed to analyze the difference of Caspase-3 immunoexpression between GCB and non-GCB subtypes of DLBCL.

Materials and Methods: Caspase-3 immunoexpression examination was performed in 41 DLBCL cases, consisted of 18 cases of GCB and 23 cases of non-GCB subtypes by using immunohistochemistry technique. The cases came from RSCM and 6 other hospitals in Jakarta.

Result: The number of GCB subtype which showed positive Caspase-3 staining was 13 cases (72%) and negative in 5 cases (28%). The number of non-GCB subtype which showed positive Caspase-3 staining was 5 cases (22%) and negative in 18 cases (78%). There was significant difference of Caspase-3 immunoexpression between GCB and non-GCB subtype of DLBCL (p = 0,002).

Conclusion: The positivity of Caspase-3 expression was higher in GCB subtype than non-GCB subtype."

"Our recent understanding of the cellular and molecular defects and the regulation of the apoptotic signalling pathways has resulted in rationally designed anticancer strategies and the development of novel agents that regulates apoptosis. A comprehensive review of all apoptotic-related anticancer therapies is not the purpose of this book. However, in the volume of this book with 11 chapters, we have described a number of novel apoptotic regulators that have shown promising value and also great feasibility for cancer treatment. These novel agents either occur naturally or are chemically synthes. "

"Selama beberapa puluh tahun terakhir, banyak peneliti mempelajari penyebab-penyebab infertilitas pria, yang difokuskan pada peranan spesies oksigen reaktif (SOR). Spesies oksigen reaktif adalah suatu zat pengoksidasi yang sangat reaktif dan tergolong dalam kelompok radikal bebas. Bila kadar SOR meningkat, maka terjadi stres oksidatif yang menghasilkan oksigen dan oksidan derivat oksigen, yang pada gilirannya meningkatkan kerusakan sel. Pada manusia, SOR diproduksi oleh beberapa komponen semen, dan antioksidan pada cairan seminalis akan menjaga keseimbangan kadar SOR tersebut. Fungsi SOR dalam jumlah sedikit akan membantu kemampuan fertilisasi spermatozoa. Banyak penelitian menunjukkan bahwa SOR menyerang integritas DNA pada nukleus sperma dengan cara modifikasi basa, memutuskan untai DNA, dan menyebabkan ?chromatin cross linking?. Kerusakan DNA meningkatkan kadar SOR dan dapat mempercepat proses apoptosis sel germinal yang berakibat menurunnya jumlah sperma yang berkaitan dengan kasus infertilitas pria. Makalah ini menelaah asal molekular/selular SOR pada semen, bagaimana SOR merusak DNA nukleus sperma, dan bagaimana kerusakan DNA berperanan dalam infertilitas pria. Peningkatan produksi SOR oleh spermatozoa berkaitan dengan penurunan potensial membran mitokondria (PMM), yang merupakan indikator penting untuk integritas fungsional spermatozoa. Apoptosis sel germinal penting untuk fungsi spermatogenesis normal dan gangguan regulasinya akan mengakibatkan infertilitas pria. Pemahaman penyebab dan mekanisme apoptosis sel germinal merupakan hal penting dalam mencegah masalah reproduksi pria. Tingkat apoptosis pada spermatozoa matang yang berkorelasi secara signifikan dengan kadar SOR cairan seminalis yang ditentukan oleh pemeriksaan kemiluminesens menunjukkan adanya hubungan antara SOR dan masalah fertilitas. (Med J Indones 2007; 16:127-33).

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Over the past few decades many researchers studying the causes of male infertility have recently focused on the role played by reactive oxygen species (ROS) ? highly reactive oxidizing agents belonging to the class of free radicals. If ROS levels rise, oxidative stress (OS) occurs, which results in oxygen and oxygen derived oxidants, and in turn increases the rates of cellular damage. In human, ROS are produced by a variety of semen components, and antioxidants in the seminal fluid keep their level balance. Small amounts of ROS help spermatozoa acquire their necessary fertilizing capabilities. Many researches showed that ROS attack DNA integrity in the sperm nucleus by causing base modification, DNA strand breaks, and chromatin cross linking. The DNA damage induced excessive levels of ROS and might accelerate the process of germ cell apoptosis leading to a decline in sperm counts associated with male infertility. This paper will review the molecular (cellular) origins of ROS in human semen, how ROS damage sperm nuclear DNA, and how such DNA damage contributes to male infertility. Increased ROS production by spermatozoa is associated with a decreased mitochondrial membrane potential (MMP), which is an important indicator of functional integrity of the spermatozoa. Germ cell apoptosis is essential for normal spermatogenesis and its dysregulation may lead to male infertility. Thus, understanding the causes and mechanisms of germ cell apoptosis is of major importance in preventing male reproductive problems. Levels of apoptosis in mature spermatozoa that were significantly correlated with levels of seminal ROS determined by chemiluminescence assay indicate the linkage between ROS and male fertility problems. (Med J Indones 2007; 16:127-33)."

"ABSTRAKLatar Belakang: Laki-laki menyumbang sekitar 40% kasus untuk infertilitas. Salah satu penyebab infertilitas yakni kasus azoospermia. Pada beberapa kasus azoospemia yang ditangani melalui teknologi reproduksi berbantu dengan kegagalan perolehan sperma dari testicular sperm extraction (TESE), maka Spermatogonial Stem Cells (SSCs) dapat menjadi salah satu alternatif terapi. SSCs dapat diperoleh dari isolasi dan kultur sel spermatogenik. Sejak abad ke 19, berbagai metode isolasi dan kultur sel spermatogenik mulai dikembangkan. Akan tetapi berbagai metode ini belum ada yang optimal. Oleh karena itu, dibutuhkan suatu teknik kultur untuk mengoptimalisasi proses ekspansi sel spermatogenik, dari segi faktor apoptosis.Metode: Pada penelitian ini dilakukan pemberian suplemen kultur berbeda pada medium kultur yakni FBS 10%, PRP 10%, dan PRP 10% ditambah faktor pertumbuhan (GDNF, bFGF, EGF) untuk proses kultur. Hasil kultur dilakukan identifikasi marka permukaan CD90 dan GFRA1 menggunkan flowsitometri dan dilakukan uji apoptosis. Fenomena apoptosis yang muncul diamati berdasar adanya fragmentasi pada DNA dengan metode TUNEL serta adanya peran eksekutor apoptosis yakni kaspase-3 yang teramati pada pengujian imunositokimia.Hasil Penelitian: Hasil analisis marka permukaan CD90 dan GFRA1 memiliki nilai berbeda- beda pada pemberian medium yang berbeda. Pertumbuhan sel kultur lebih baik dengan indeks apoptosis yang lebih rendah pada medium dengan pemberian PRP dan PRP ditambah faktor pertumbuhan (FBS= 25.01%, PRP = 9.99%, PRP+ GF= 2.47%). Nilai ekspresi kaspase-3 pada sel yang diberi suplemen FBS sekitar 21%, PRP 13% dan PRP + GF 7%.Kesimpulan: PRP lebih baik dibandingkan dengan FBS sebagai medium kultur sel spermatogenik, dari segi apoptosis.

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ABSTRACTBackground: Males contribute to 40% of the infertility cases over the universe. One of the causes of men infertility is azoospermia. In some cases of azoospemia which are handled through assisted reproductive technology with the failure of sperm retrieval from testicular sperm extraction (TESE), the Spermatogonial Stem Cells (SSCs) could be an alternative therapy. SSCs can be obtained from isolation and culture of spermatogenic cells. Since the 19th century, various methods of isolation and spermatogenic cell culture began to be developed. However, there are not optimal condition of this yet. Therefore, we need to optimize the spermatogenic cell expansion method, particularly in apoptotic factor.Method: In this study, the culture system were administrated by thesupplementation with 10% FBS, 10% PRP, and 10% PRP plus growth factors (GDNF, bFGF, FGF). Spermatogenic cells were identified the surface markers CD90 and GFRA1 using flowsitometry and apoptosis tests were performed. The apoptotic phenomenon was observed based on the presence of DNA fragmentation by the TUNEL method and the caspase-3 expression by immunocytochemical.Result: The result of surface marker had different value. The results showed better that cell culture growth and lower apoptotic index in the medium with PRP and PRP+ GF (FBS= 25.01%, PRP= 9.99%, PRP+ GF= 2.47%). Immuno-expression of caspase-3 in cells cultured with FBS 21%, PRP 13%, dan PRP+ GF 7 %.Conclusion: PRP was better than FBS as the spermatogenic cell culture medium based on apoptotic phenomenon."

"Gastric epithelial cells apoptosis induced by Helicobacter pylori depends on microhial and host factors. Apoptosis on mitochondrial level by Bc!2 family protein is the main pathway for Helicobacter pylori induced gastric epithelial cells apoptosis, though there are roles for apoptosis through Fas receptors or TNF. Imbalance between proliferation and apoptosis gastric epithelial cells determines the risk for neoplastic transformation. Increase of gastric epithelial cells apoptosis seems to have an obligation for initiating secondary hyperproliferative response. If altruistic cellular death fails to oppose this process, uncontrollable cellular growth leading to neoplastic transformation will occur."

"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."

"Kejadian kanker kolon mayoritas terjadi secara sporadik. Berbagai faktor non-inherited yang dipikirkan sebagai penyebab kanker kolon merupakan kombinasi antara faktor diet dan lingkungan. Kedua faktor ini menyebabkan mutasi somatik pada berbagai gen spesifik dalam pembentukan kanker kolon. Di antara berbagai faktor, butirat (dibentuk dalam proses fermentasi fiber) mungkin mempunyai peranan yang penting sebagai zat kemoprotektif terhadap kanker kolon. Sumber butirat dalam makanan sehari-hari berasal dari makanan yang mengandung kulit gandum. Pada tingkat molekuler, butirat menyebabkan asetilasi histon, meningkatkan diferensiasi berbagai sel, menginduksi terjadinya apoptosis dan meregulasi ekspresi dari berbagai onkogen. Faktor-faktor ini yang menjadi alasan butirat mempunyai efek protektif terhadap kanker kolon. (Med J Indones 2003; 12: 127-31)

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The majority of colon cancers occur sporadically. They are thougth to be caused by non-inherited factors such as a combination of diet and environmental factors, which result in somatic mutations of specific genes. Among dietary factors butyrate which is derived from fermentable fibers may have important role as chemoprotector against colorectal cancer. The source of butyrate in daily diet mostly come from wheat products especially wheat bran. At molecular level, butyrate causes hystone acetylation, favours differentiation, induces apoptosis and regulates the expressions of various oncogens. These effects suggest that butyrate may be protective against colorectal cancers. (Med J Indones 2003; 12: 127-31)"