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"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."

"[Pendahuluan: Proses karsinogenesis adenokarsinoma prostat terjadi akibat disregulasi kadar zinc dalam sel. Molekul zinc intrasel berperan dalam metabolisme aerob mitokondria dan induksi apoptosis. Penyerapan zinc diatur oleh protein ZIP1, berperan meningkatkan kandungan zinc sitoplasmik intrasel dengan membawa zinc dari cairan ekstrasel. Kadar zinc yang tinggi dan ekspresi protein ZIP1 banyak ditemukan pada epitel prostat normal, sedangkan pada kanker prostat ditemukan sedikit atau tidak ada ekspresi protein ZIP1. Penurunan ekspresi ZIP1 diduga dapat menghambat apoptosis, serta memacu perkembangan adenokarsinoma prostat. Penelitian ini bertujuan menganalisis korelasi ekspresi protein ZIP1 dan Caspase- 3 pada jaringan adenokarsinoma prostat berdasarkan Gleason score yang berbeda. Metode: Desain studi analitik retrospektif dengan desain potong lintang. Sampel penelitian ini adalah 31 sediaan blok parafin adenokarsinoma prostat yang memenuhi kriteria inklusi. Sediaan dipulas menggunakan teknik imunohistokimia untuk mengetahui ekspresi protein ZIP1 dan caspase-3. Ekspresi protein pada pulasan slide dihitung menggunakan program imageJ. Gleason score sebagai data sekunder yang didapatkan dari laporan kasus. Korelasi ekspresi kedua protein berdasarkan Gleason score dianalisis dengan uji korelasi Pearson menggunakan SPSS 11.5. Hasil: Rerata positivitas ekspresi ZIP1 pada adenokarsinoma prostate adalah 35% dan rerata positivitas caspase-3 adalah 33%. Terdapat korelasi positif bermakna antara ekspresi ZIP1 dan caspase-3 (r = 0.379 , p = 0,018). Terdapat korelasi positif antara ekspresi ZIP1 dan caspase-3 pada kelompok intermediate grade (r = 0.73, p = 0.01) dan korelasi lemah tidak bermakna pada kelompok high grade (r = 0.04, p = 0.48). Kesimpulan: Terdapat korelasi positif antara ekspresi ZIP1 dan ekspresi caspase- 3 pada adenokarsinoma prostat.

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, Introduction: Carcinogenesis of adenocarcinoma of the prostate occurs due to dysregulation of zinc level within the cells. Intracellular zinc molecules contributes to mitochondrial aerobic metabolism. Its influx is regulated by a transporter protein ZIP1, whose non-presence is predicted to inhibit apoptosis, thus leads to the development of prostate adenocarcinoma. This study was aimed to analyze the correlation of ZIP1 and Caspase-3 expression in prostate adenocarcinoma with respect to its grading as represented by Gleason Score. Methods: This was a cross-sectional, retrospective analytical study on 31 formalyn-fixed, paraffin-embedded tissue that meet inclusion criteria. The specimen was stained using immunohistochemical technique for ZIP1 and Caspase-3. Protein expression of each case were counted using ImageJ analysis. Gleason score were acquired as secondary data from the cases’ reports. The correlation of their expression with respect of Gleason score were analyzed with Pearson’s correlation using SPSS 11.5.

Results: Mean expression level of ZIP1 and Caspase-3 in prostate adenocarcinoma were 35% and 33%, respectively. There was a significantly positive correlation between ZIP1 and Caspase-3 expression (r=0.379; p=0.018). However, their correlation was stronger in intermediate-grade group (r=0.73; p=0.01) and the correlation was much weaker in high-grade group (r=0.04; p=0.48).

Conclusion: There was a positive correlation between ZIP1 and caspase-3 expression in adenocarcinoma prostate.]"

"Pendahuluan: Tingkat kematian pasien kanker payudara menempati posisis tertinggi dunia dan umum terjadi pada wanita. TNBC merupakan jenis kanker payudara yang memiliki prognosis buruk. Selain tidak memiliki reseptor hormonal (ER, PR, dan HER2), TNBC memiliki kemampuan yang tinggi dalam mempertahankan hidup dan menolak apoptosis. Hal ini berkaitan dengan tingginya ekspresi gen Survivin, sebagai protein IAP (inhibitor apoptosis protein) yang berperan dalam menghambat apoptosis dan meningkatkan proliferasi. Studi terbaru menunjukkan bahwa CRISPR/Cas9 merupakan pendekatan yang sesuai untuk mengedit gen yang berpeluang besar dalam terapi kanker.Bahan dan Metode: Sel TNBC BT549 yang telah ditransfeksi dengan Cas9 dan sgRNA. Analisis molekuler dimulai dengan analisis aktifitas pembelahan gen menggunakan (PCR), efisiensi pengeditan genom (Sanger Sequencing), ekspresi mRNA Survivin (qRT-PCR), dan analisis ekspresi protein Survivin (westernblot). Analisis fenotipe dilakukan dengan uji apoptosis (flowcytometry) dan proliferasi (tripan-blue exclusion assay). Analisis bioinformatika dilakukan dengan menganalisis struktur protein (PyMoL) dan analisis interaksi protein (Cytoscape).Hasil: CRISPR/Cas9 berhasil menghilangkan fungsi gen Survivin pada sel TNBC BT549. Penurunan ekspresi mRNA dan protein Survivin signifikan, peningkatan apoptosis dan penghambatan proliferasi pada sel TNBC BT549.Kesimpulan: Penelitian ini merupakan riset pertama kali yang berhasil membuktikan efek dari KO Survivin pada apoptosis dan proliferasi sel TNBC BT549.

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Introduction: Breast cancer has the highest mortality rate in the world and is most common in women. TNBC is a type of breast cancer with a poor prognosis. TNBC, in addition to lacking hormonal receptors (ER, PR, and HER2), has a high ability to maintain life and resist apoptosis. This is due to the high expression of the Survivin gene, an apoptotic inhibitor protein that plays a role in inhibiting apoptosis and increasing proliferation. Recent research has shown that CRISPR/Cas9 is a suitable approach for gene editing with great potential in cancer therapy.

Materials and Methods: Cas9 and sgRNA were transfected into BT549 TNBC cells. Molecular analysis with PCR, genome editing efficiency (Sanger Sequencing), Survivin mRNA expression (qRT-PCR), and protein expression analysis (westernblot). Phenotypic analysis were carried out by apoptosis (flowcytometry) and proliferation (trypan-blue exclusion assay). Protein structure were studied using (PyMoL) and protein interaction (Cytoscape).

Results: CRISPR/Cas9 successfully eliminated the function of the Survivin gene in BT549 TNBC cells. Significant reduction in Survivin mRNA and protein expression, increased apoptosis, and inhibition of proliferation in BT549 TNBC cells.

Conclusion: This study is the first to demonstrate the effect of Survivin knockout on apoptosis and proliferation of TNBC BT549 cells."

"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."