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Abstrak :
Kanker paru merupakan salah satu penyebab terbanyak kematian akibat kanker di Indonesia. Namun, terapi kanker konvensional memiliki kelemahan seperti efek samping terhadap tubuh dan tingginya biaya yang dibutuhkan. Oleh karena itu, studi mengenai pengobatan alternatif kanker menggunakan tumbuhan herbal mulai banyak dilakukan. Bunga rosela merah (Hibiscus sabdariffa) sebagai salah satu tanaman herbal di Indonesia diketahui memiliki aktivitas biologis, namun penelitiannya masih terbatas. Penelitian ini dilakukan untuk mengetahui kandungan fitokimia, aktivitas antioksidan, dan aktivitas sitotoksik bunga rosela merah secara in vitro terhadap sel kanker paru A549. Penelitian eksperimental ini diawali dengan maserasi sampel dalam pelarut etanol, etil asetat, dan n-heksana. Kemudian, dilakukan uji kromatografi lapis tipis dan uji fitokimia untuk mengetahui kandungan metabolit sekundernya. Aktivitas antioksidan dari ekstrak ditentukan dengan metode DPPH, sedangkan aktivitas sitotoksik dari ekstrak terhadap sel kanker paru A549 ditentukan dengan uji MTT assay secara invitro. Hasil uji kromatografi lapis tipis menunjukkan terdapat lima komponen senyawa, sedangkan hasil uji fitokimia memberikan hasil positif untuk flavonoid, tanin, glikosida, alkaloid, triterpenoid, dan steroid. Uji aktivitas antioksidan untuk ekstrak etanol dan etil asetat Hibiscus sabdariffa memberikan nilai IC50 lebih dari 50 g/mL. Sementara itu, uji sitotoksik in vitro ekstrak etanol, etil asetat dan n-heksana Hibiscus sabdariffa terhadap sel kanker paru A549 memberikan nilai IC50 lebih dari 200 g/mL. Kesimpulan dari penelitian ini adalah ekstrak Hibiscus sabdariffa memiliki aktivitas antioksidan yang tergolong lemah hingga moderat, dan menunjukkan aktivitas sitotoksik yang tergolong lemah terhadap sel kanker paru A549, sehingga ekstrak Hibiscus sabdariffa berpotensi untuk dikembangkan sebagai antioksidan dan agen antikanker paru.

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Lung cancer is one of the leading causes of cancer death in Indonesia. Treatment for lung cancer has side effects and requires high cost. Therefore, the study concerning natural anticancer from plants has intensified, in this study focused on Hibiscus sabdariffa. The purpose of this research is to evaluate the phytochemistry composition, antioxidant activity, and cytotoxic activity of Hibiscus sabdariffa extracts against the A549 lung cancer cell line. The research was carried out by macerated the sample with ethanol, ethyl acetate, and n-hexane solvents. The extracts were analyzed using TLC and phytochemistry tests to determine secondary metabolites. The antioxidant activity of the extract was determined using the DPPH method, while the cytotoxic activity of the extract against the A549 lung cancer cells was determined in vitro using the MTT assay. As a result, the TLC analysis revealed that Hibiscus sabdariffa extracts contained five organic compounds, while the phytochemistry tests revealed positive for flavonoids, tannins, glycosides, alkaloids, triterpenes, and steroids. The antioxidant activity test of the ethanol and ethyl acetate extracts showed the IC50 value of more than 50 g/mL. Furthermore, the cytotoxic activity of the ethanol, ethyl acetate, and n-hexane extract against the A549 lung cancer cell line showed the IC50 value of more than 200 g/mL. In conclusion, Hibiscus sabdariffa extracts had the low to moderate antioxidant activity and the weak anticytotoxic activity against the A549 lung cancer cell line, so Hibiscus sabdariffa extracts are potential to be developed as antioxidant and anticancer.

Abstrak :
In recent years, cancer stem cells have been recognized as important component in carcinogenesis and they seem to form the basis of many (if not all) tumor types. Cancer stem cells or "cancer cell like stem cells" have been isolated from various cancers of different origin (blood, breast, brain, skin, head and neck, thyroid, cervix, lung, retina, colon, pancreas and so on). Cancer stem cells - rare cells with indefinite proliferative potential that drive the formation and growth of tumours- seem to show intriguing relationships with physiological stem cells. Specifically, these cancer cells show significant similarities in the mechanisms that regulate self-renewal of normal stem cells. Moreover, tumour cells might directly arise from normal stem cells. Further, the cellular biology of cancer stem cells show a lot of similarities with normal stem cells.

Abstrak :
Difference between tissue specific stem cells and embryonic stem cells is explained. The advantages of the latter are included. The application of human pluripotent stem cells, mesenchymal stem cells, and hematopoietic stem cells in cancer therapy and tissue/organ regeneration is detailed. Role of neural cancer stem cells in brain tumors, including their role in brain tumor therapy and the role of CD133 stem cell antigen in glioma patients, is emphasized. Therapeutic role of bone marrow-derived stem cells in myocardial infarction and the role of mesenchymal stem cells in orthopedics are explained. Transplantation of umbilical cord hematopoietic stem cells and allogeneic hematopoietic stem cell transplantation followed by graft-versus-host disease are presented. Role of cancer stem cells specifically in glioblastoma and medulloblastoma is included. It is also emphasized that CD133 is an appropriate stem cell marker for gliomas. Targeting of cancer cells is also explained.

Abstrak :
It is pointed out that cancer stem cell is a cell type within a tumor that possesses the capacity of cell-renewal and can give rise to the heterogeneous lineages of cancer cells that comprise the tumor. It is emphasized that a cancer stem cell is a tumor initiating cell. That conventional chemotherapy kills most cells in a tumor, but cancer stem cells remain intact is discussed. Vast applications of stem cells, cancer stem cells, mesenchymal stem cells, and human pluripotent stem cells are discussed. Because human embryonic stem cells possess the potential of producing unlimited quantities of any human cell type, considerable focus is placed on their therapeutic potential in this volume. Because of the pluripotency of embryonic stem cells, this volume discusses various applications such as tissue engineering, regenerative medicine, pharmacological and toxicological uses. The role of these cells in cell differentiation is also included. The role of cancer stem cells of breast, colon, and melanoma tumors in response to antitumor therapy is detailed. The role of cancer stem cells, specifically in the deadliest brain cancer, glioblastoma multiforme, is explained. Transplantation of bone marrow-derived stem cells for myocardial infarcation and use of mesenchymal stem cells in orthopedics are described.

Abstrak :
Vast therapeutic applications of the following specific stem cells in disease and tissue injury are discussed, embryonic stem cells, induced pluripotent stem cells, human hair follicle stem cells, bone marrow-derived human mesenchymal stem cells, adipose-derived stem cells, periodontal/progenitor cells, cancer stem cells, and breast cancer stem cells. Because human embryonic stem cells possess the potential to produce unlimited quantities of any human cell type, considerable focus is placed on this type of stem cells in this volume. The role of cancer stem cells, specifically in breast cancer is explained. Transplantation of mesenchymal stem cells to aid the injured brain is included. Immune recovery after stem cells transplantation in severe combined immunodeficiency patients is described. The role of mesenchymal stem cells in enhancing the growth and metastasis of colon cancer is discussed. Clinical application of human follicle stem cells is presented. Treatment of malignant gliomas using genetically-modified neural stem cells as a marker is discussed. The impact of cancer stem cell hypothesis on designing new cancer therapies is explained. In the field of regenerative medicine, the use of stem cells in the repair of the central nervous system, tendon injury, and as a cardiac regenerative medicine is described. The role of DNA methylation in maintaining stemness induced pluripotent stem cells from human extraembryonic amnion cells is discussed. Insights on the understanding of molecular pathways involved in tumor biology are explained, which lead to the development of effective drugs. Information on pathways, such as hedgehog, facilitates targeted therapies in cancer.

Abstrak :
It is pointed out that a cancer stem cell is a type within a tumor that possesses the capacity of self-renewal and can give rise to the heterogeneous lineages of cancer cells, which comprise the tumor. It is emphasized that a unique feature of cancer stem cells is that, although conventional chemotherapy kills most cells in a tumor, cancer stem cells remain intact. Vast applications of the following specific stem cells in disease and tissue injury are discussed: embryonic stem cells, human mesenchymal stem cells, cancer stem cells, arterial stem cells, neural stem cells, cardiac stem cells, dental stem cells, limbal stem cells, and hematopoietic stem cells. Because human embryonic stem cells possess the potential to produce unlimited quantities of any human cell type, considerable focus is placed on their therapeutic potential in this volume. These cells are used in tissue engineering, regenerative medicine, pharmacological and toxicological studies, and fundamental studies of cell differentiation. It is pointed out that the formation of embryoid bodies, which are three-dimensional aggregates of embryonic cells, is the initial step in the differentiation of these cells. Therapeutic implications of signalling pathways in cancer stem cells are pointed out. Targeting self-renewal pathways in cancer stem cells are also included. Application of mesenchymal stem cells for treating ischemic brain injury is explained. Neural stem cells proliferation into the surrounding area of the traumatic brain injury is explained.

Abstrak :
The difference among pluripotent stem cells, multipotent stem cells, and unipotent stem cells is pointed out. Vast therapeutic applications of the following specific stem cells in disease and tissue injury are discussed: human embryonic stem cells, human mesenchymal stem cells, germ cell-derived pluripotent stem cells, induced pluripotent stem cells, human umbilical cord blood-derived stem cells, breast tumor stem cells,and hematopoietic stem cells. Because of the potential of human embryonic stem cells to produce unlimited quantities of any human cell type, considerable focus is placed on their therapeutic potential. Because of their pluripotency, these cells have been used in various applications such as tissue engineering, regenerative medicine, pharmacological and toxicological studies, and fundamental studies of cell differentiation. The formation of embryoid bodies, which are three-dimensional aggregates of embryonic stem cells, is explained as this is the first step in cell differentiation. Such embryoid body culture has been widely used as a trigger for the in vitro differentiation of embryonic stem cells. The basic capacity of self-renewal of human embryogenic stem cells is explained. The role of TGF-beta in the propagation of human embryonic stem cells is discussed. The differentiation of human embryonic stem cells into neurons, hepatocytes, cardiomyocytes, and retinal cells is fully explained. Donor policies for hematopoietic stem cells are also explained.

Abstrak :
Hipoksia merupakan salah satu faktor penyulit dalam pemberian terapi radiasi, di mana kondisi kekurangan oksigen pada jaringan tumor dapat mengurangi sensitivitasnya terhadap radiasi. Di sisi lain, saat ini perkembangan imunoterapi dalam terapi kanker sangatlah pesat, termasuk blokade immune checkpoint PD-L1, yang dianggap menjadi harapan baru bagi terapi kanker. Ekspresi PD-L1 telah diketahui meningkat setelah pemberian radiasi, sehingga dapat menjadi dasar pemberian imunoterapi dalam kombinasi dengan radiasi. Regulasi PD-L1 ini terutama diatur melalui jalur-jalur transduksi sinyal perbaikan DNA. Dalam kondisi hipoksia, belum banyak diketahui bagaimana respon PD-L1 pada sel kanker dengan atau tanpa radiasi. Dikaitkan dengan jalur perbaikan DNA, telah banyak studi yang meneliti pengaruh hipoksia terhadap jalur-jalur ini. Namun, belum ditelaah atau diteliti secara langsung pengaruh ini terhadap regulasi ekspresi PD-L1 pada sel. Studi ini merupakan studi eksplorasi awal pada bidang ini yang bertujuan untuk meneliti ekspresi PD-L1 pada kultur sel beberapa cell lines kanker (U2OS, A549, DU145, OE21) secara in vitro dengan perlakuan radiasi sinar X (5, 10, atau 20 Gy) dalam kondisi inkubasi hipoksia atau dalam perlakuan hipoksia saja selama 2, 24, 48, atau 72 jam. Data awal ini juga dilengkapi dengan analisis bioinformatika menggunakan data The Cancer Genome Atlas (TCGA) yang memperlihatkan perbedaan ekspresi PD-L1 pada peningkatan ekspresi HIF1α pada dataset yang hipoksik dan yang tidak. Pada seluruh cell lines yang diteliti, tidak tampak peningkatan ekspresi PD-L1 dalam inkubasi hipoksia (dengan kadar oksigen 0,5%, 0,1%, dan <0,1%) dengan ataupun tanpa radiasi X-ray. Analisis in silico menunjukkan bahwa korelasi positif antara kadar mRNA PD-L1 dan marker-marker hipoksia tampak lebih menonjol pada dataset yang tidak hipoksik dibandingkan yang paling hipoksik. Selanjutnya, perbedaan kadar HIF1A menunjukkan perbedaan kadar ekspresi PD-L1 yang signifikan hanya pada dataset yang tidak hipoksik, terutama pada sampel tanpa mutasi gen-gen DNA repair yang diteliti. Temuan ini dapat menjadi argument bahwa HIF1A tidak selalu dapat meningkatkan ekspresi PD-L1, terutama pada tumor-tumor yang sangat hipoksik. ...... Hypoxia is one of adverse clinical prognosis factors in patients receiving radiation treatment, where oxygen deprivation in tumor tissue is known to reduce its sensitivity to radiation. While in the field of cancer treatment, immunotherapy has been rapidly advancing, including the blockade of immune checkpoint PD-L1, eliciting new hope in the horizon. PD-L1 expression interestingly has been reported to increase after irradiation, which may become a rationale for combining radiation and immunotherapy. This upregulation of PD-L1 is mainly conducted via DNA repair pathways. However, in hypoxic condition, not much is know on how PD-L1 expressions in cancer cells respond, with or without irradiation. In view of many reports of hypoxic modulation of DNA repair pathways, there has been no study to date that analyzes or reports specifically on how this modulation impacts regulation of PD-L1 expression in cells. This study aims to serve as a pilot explorative study in this exploration, which is to analyze PD-L1 expression in cell cultures of several human cancer cell lines (U2OS, A549, DU145, OE21) in vitro in hypoxia incubation (2, 24, 48, or 72 hours) with or without X-ray irradiation (5, 10, or 20 Gy). This primary data was also completed with bioinformatics analysis using The Cancer Genome Atlas (TCGA) database, which showed difference in PD-L1 expression in samples with higher expression of HIF1α between hypoxic and non-hypoxic datasets. In all cell lines used, there was no upregulation of PD-L1 expression after hypoxia incubation (in oxygen levels 0,5%, 0,1%, and below 0,1%) with or without X-ray irradiation. Although in silico analysis of TCGA databases showed positive correlation of PD-L1 and hypoxia markers mRNA levels, these were seen more prominently in non-hypoxic datasets compared to the most-hypoxic datasets. Further, differences in HIF1A levels showed very significant difference in PD-L1 expression only in nonhypoxic datasets, especially in samples without mutation in DNA repair genes. These results may propose the argument that HIF1A does not always promote PD-L1 expression, especially in very hypoxic tumors.

Abstrak :
This volume sets out to cover a staggering range of research into the medical applications of stem cell research. While stem cells are the very stuff of life for multicellular organisms, including us humans, the cancer stem cell is a morbid entity with a robust resistance to therapies including conventional chemotherapy. This authoritative publication explains the regenerative potential of stem cells and their mesenchymal progeny, reviewing clinical applications of the latter in the treatment of cancer, diabetes and neurodegenerative pathologies. It covers the entire range of stem cells with known potential for therapeutic use, from human embryonic to germ cell-derived pluripotent stem cells and hematopoietic stem cells. The chapters also deal with the role of TGF-beta in propagating human embryonic stem cells, and in facilitating their differentiation. Featuring discussions of molecular signaling pathways that modulate mesenchymal stem cell self-renewal and much more.

Abstrak :
This book provides an overview of critical components of cell signaling machinery and its role in epithelial morphogenesis, proliferation, invasions and angiogenesis in human cancer and discusses novel types of protein kinase pathways.