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Abstrak :
Latar Belakang: Perubahan genetik pada p53 menyebabkan imortalisasi dan kecenderungan sel bertransformasi menjadi neoplasma. Imortalisasi ini berhubungan dengan pemeliharaan panjang telomer oleh telomerase. hTERT adalah komponen kunci telomerase yang aktivitasnya ditekan oleh p53. Tujuan: Menganalisis profil protein hTERT pada sel galur KSSRM HSC-3 dan HSC-4 serta jaringan mukosa mulut normal. Metode: Profil protein hTERT dianalisis menggunakan teknik SDS-PAGE dan Gel Doc, Quantity One. Hasil: Protein hTERT diekspresikan oleh sel galur KSSRM mulut tipe HSC 3 dan HSC 4 serta 2 dari 17 sampel protein jaringan mukosa mulut normal. Simpulan: Protein hTERT yang diekspresikan oleh sel galur KSSRM berhubungan dengan kondisi mutan p53. Adanya ekspresi protein hTERT pada jaringan mukosa mulut normal diperkirakan karena adanya sel keratinosit dan infiltrasi sel hematopoietik.

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Backround: Genetic alteration on p53 allows cellular immortalization and predisposes cells to neoplastic transformation. This immortalization is related to telomere length maintenance by telomerase. hTERT is a key component of telomerase, which activity is suppressed by p53. Objectives: To analyze the hTERT protein profile in HSC-3 and HSC-4 OSCC cell lines and normal human oral mucosa tissue. Methods: SDS-PAGE and Gel Doc, Quantity One were used for analyzing hTERT protein profile. Results: hTERT protein expressed in HSC-3 and HSC-4 OSCC cell lines and 2/17 protein samples of normal human oral mucosal tissues. Conclusion: hTERT protein that was expressed by OSCC cell lines is related to their status of mutant p53. The existing of hTERT protein on normal human oral mucosas tissue may be caused by keratinocyte cells and infiltrated hemapoietic cells.

Abstrak :
Kanker kolorektal merupakan keganasan sel yang tumbuh dari jaringan usus besar, seperti kolon dan rektum. Kasus kanker kolorektal di Indonesia menempati urutan ketiga dengan 12,8 insiden per 100.000 penduduk usia dewasa dan memiliki nilai mortalitas sebesar 9,5% dari seluruh kasus jenis kanker. Lambatnya diagnosis kanker sejak dini dan prognosis yang buruk menyebabkan tingginya mortalitas kanker kolorektal di Indonesia dibandingkan pada beberapa negara maju. Oleh karena itu, diperlukan identifikasi biomarker, seperti deteksi ekspresi RNA yang berfungsi sebagai pemberi informasi genetik dan subjek regulasi transkripsi, untuk memahami jalur pensinyalan karsinogenesis kolorektal dalam meningkatkan prognosis dan prediksi respons terapeutik terhadap pasien. Telomerase Reverse Transcriptase (hTERT) merupakan subunit utama dari enzim telomerase yang memiliki peran dalam menjaga kestabilan kromosom, sehingga mengindikasi adanya pengaruh ekspresi hTERT yang tinggi terhadap perkembangan kanker kolorektal. Penelitian ini menggunakan sampel jaringan normal dan kanker kolorektal yang diperoleh dari pasien pengidap kanker kolorektal dengan nilai ekspresi gen hTERT diperoleh menggunakan reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Nilai Cycle Threshold (CT) diperoleh dan dilakukan analisis statistik menggunakan aplikasi JAMOVI. Berdasarkan rumus ekspresi gen 2-IICT, ekspresi meningkat jika memiliki perhitungan ekspresi <1 dan ekspresi menurun jika memiliki perhitungan ekspresi 1<. Hasil menunjukkan bahwa sebesar 50% pasien pengidap kanker kolorektal mengalami peningkatan ekspresi gen hTERT RNA, sedangkan 50% lainnya mengalami penurunan ekspresi. Peningkatan ekspresi gen hTERT RNA pada jaringan kanker adalah sebesar 18,97 kali lebih tinggi dibandingkan jaringan normal. Namun, berdasarkan analisis statistik, ekspresi hTERT tidak menunjukkan perbedaan yang signifikan antara jaringan normal dan kanker dikarenakan jumlah sampel yang sedikit. ......Colorectal cancer is a malignancy that grows from the tissues of the large intestine, such as the colon and rectum. Colorectal cancer cases in Indonesia ranks third with 12.8 incidents per 100,000 adult population and has a mortality rate of 9.5% of all cancer cases. The delay in early cancer diagnosis and poor prognosis lead to higher colorectal cancer mortality in Indonesia compared to some developed countries. Therefore, it is necessary to identify biomarkers, such as detection of RNA expression that serves as a genetic information provider and transcriptional regulatory subject, to understand the signaling pathways of colorectal carcinogenesis in improving prognosis and predicting therapeutic response in patients. Human Telomerase Reverse Transcriptase (hTERT) is the main subunit of the telomerase enzyme that has a role in maintaining chromosome stability, thus indicating the effect of high hTERT expression on the development of colorectal cancer. This study used normal tissue samples and colorectal cancer obtained from patients with colorectal cancer with hTERT gene expression values ​​obtained using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cycle Threshold (CT) values ​​were obtained, and statistical analysis was performed using the JAMOVI application. Based on the 2-IICT gene expression formula, the expression increased if it had an expression count <1 and the expression decreased if it had an expression count of 1<. The results showed that 50% of patients with colorectal cancer had an increased expression of the hTERT RNA gene, while the other 50% had decreased expression. The increase in hTERT RNA gene expression in cancer tissue was 18.97 times higher than normal tissue. However, based on statistical analysis, hTERT expression did not show a significant difference between normal and cancer tissues due to the small number of samples.

Abstrak :
Radiasi merupakan terapi pilihan untuk kanker serviks stadium III B, namun permasalahan timbul karena adanya sifat radioresisten. Sel punca kanker SPK merupakan salah satu faktor yang diduga berkontribusi terhadap hal tersebut. SOX2 dan OCT4 merupakan faktor transkripsi yang mengekspresikan sifat-sifat SPK, yaitu mengontrol sifat pluripoten, self-renewal, berperan pada karsinogenesis, metastasis, resistensi terhadap terapi dan rekurensi tumor. Faktor apoptosis, DNA repair dan telomerase merupakan mekanisme yang berkaitan dengan radioresisten. Penelitian ini bertujuan untuk mempelajari hubungan antara SOX2 dan OCT4 sebagai penanda SPK terhadap respons terapi radiasi, serta kaitannya dengan faktor apoptosis caspase-3 , DNA repair Chk1 dan telomerase hTERT .Penelitian ini merupakan case control, terhadap 48 kasus karsinoma sel skuamosa serviks stadium III B yang telah menjalani terapi radiasi/kemoradiasi di RS Cipto Mangunkusumo/FKUI. Kasus dibagi dalam 2 kelompok, yaitu hasil terapi komplet 27 kasus dan hasil terapi inkomplet 21 kasus . Kasus dengan respons awal terapi radiasi baik dilakukan pemeriksaan bulan Pap smear dan HPV pada bulan ke-6 atau sampai ke-12 setelah terapi. Ekspresi SOX2, OCT4, caspase-3, Chk1 dan hTERT diperiksa secara imunohistokimia dari blok parafin biopsi awal.Ekspresi kuat SOX2 dan OCT4 dengan H-score masing-masing lebih dari 96,6 dan 61,9 mempunyai hubungan bermakna dengan respons awal terapi radiasi maupun respons akhir terapi radiasi SOX2 p = 0,017, p = 0,004 dan OCT4 p < 0,001, p < 0,001 . Ditemukan hubungan bermakna antara ekspresi Chk1 dan hTERT dengan respons awal terapi radiasi Chk1 p = 0,006, hTERT p = 0,029 . Tidak ditemukan hubungan yang bermakna antara ekspresi caspase-3, Chk1, hTERT dengan ekspresi SOX2 dan OCT4. Uji multivariat menunjukkan bahwa SOX2 dan OCT4 yang paling memengaruhi respons terapi OR = 5,12, p = 0,040 dan OR = 17,03, p < 0,001, secara berurutan . Uji probabilitas menunjukkan kemungkinan respons akhir terapi radiasi inkomplet sebesar 87,91 bila ekspresi kedua penanda SPK kuat.Ekspresi kuat SOX2 dan OCT4 dapat memprediksi hasil terapi radiasi inkomplet pada karsinoma serviks stadium III B. ...... Radiotherapy is the main choice of treatment for stage III B cervical cancer, but radioresistance becomes a difficult matter. Cancer stem cell is one of the factors suspected involving in radioresistant cancers. SOX2 and OCT4 are transcription factors which have pluripotent cell characteristics, and self renewal ability. They also involved in carcinogenesis, metastasis, tumor recurrent, and resistance toward therapy. Apoptotic, DNA repair, and telomerase factors are mechanisms that also contribute to radioresistance. This study aims to know the role of SOX2 and OCT4 as CSC markers, apoptotic factor caspase 3 , DNA repair Chk1 and telomerase hTERT toward radiotherapy.The design of this study was case control with 48 cases of stage III B cervical squamous cell carcinoma patients who had finished receiving radiation chemo radiation therapy at Cipto Mangunkusumo Hospital FMUI, Jakarta. They were classified in 2 groups based on the final response of treatment, which were complete and incomplete one. Pap smear and DNA HPV were performed in month 6 or until month 12 after therapy for good initial therapy. Immunohistochemistry was done to analyze SOX2, OCT4, caspase 3, Chk1 and hTERT expression from the paraffin block of initial biopsy.Strong expression of SOX2 and OCT4 with each H score was higher than 96.6, and 61.9 had significant association with both initial and final therapy response SOX2 p 0.017, p 0.004 and OCT4 p 0.001, p 0.001, repectively . There was significant association between expression of Chk1 and hTERT, and initial therapy response p 0.006 for Chk1, and p 0.029 for hTERT . No significant differences were found between caspase 3, Chk1, hTERT, and SOX2 and OCT4. Multivariate analysis showed SOX2 and OCT4 were the most influenced antibodies for radiotherapy response OR 5.12, p 0.040, and OR 17.03, p 0.001, respectively . The likelihood of incomplete final therapy response was 87.91 if the expression both of CSC markers were strong.Expression of SOX2, and OCT4 could predict the incomplete radiotherapy of stage III B cervical cancer cases.