Ide proposal penelitian

Perbandingan 2 year disease free survival rate pada pasien Ca sel transitional Buli
yang mendapatkan ekstrak curcuma dan ekstrak daun sirsak harian

Di Indonesia berdasarkan pendataan hasil pemeriksaan jaringan yang dilakukan

selama 3 tahun diketahui bahwa kanker buli-buli menempati urutan kesepuluh dari
tumor ganas primer pada pria. Di subbangian Urologi RSUPN Dr. Cipto
Mangunkusumo darii 152 kasus keganasan urologi antara tahun 1995-1997,
36% diantaranya adalah kanker buli-buli dan juga menempati urutan pertama.
The recurrence rate for superficial TCC of the bladder is high. As many as 80% of
patients have at least 1 recurrence.
The most significant prognostic factors for bladder cancer are grade, depth of
invasion, and the presence of CIS. In patients undergoing radical cystectomy for
muscle-invasive bladder cancer, the presence of nodal involvement is the most
important prognostic factor. To date, there is no convincing evidence of genetic
factors affecting outcome.[49]
Nonmuscle invasive bladder cancer has a good prognosis, with 5-year survival
rates of 82-100%. The 5-year survival rate decreases with increasing stage, as
follows:
Ta, T1, CIS 82-100%
T2 63-83%
T3a 67-71%
T3b 17-57%
T4 0-22%
Prognosis for patients with metastatic urothelial cancer is poor, with only 5-10% of
patients living 2 years after diagnosis.
The risk of progression, defined as an increased tumor grade or stage, depends
primarily on the tumor grade, as follows:
Grade I 2-4%
Grade II 5-7%
Grade III 33-64%

The high rate of disease recurrence and progression in nonmuscle-invasive bladder

cancer underscores the need for careful follow-up studies. According to the US
National Cancer Institute, bladder cancer affects approximately 500,000 people in
America. Because most still have an intact bladder, the number of patients under
surveillance approaches this figure.
The 2011 EAU guidelines include schedules for follow-up cystoscopy, urinary
cytology, and imaging in patients with TaT1 tumors, depending on risk of recurrence
and progression. For follow-up in patients with no visible tumor in the bladder but
positive cytology, the guidelines recommend biopsies and investigation of
extravesical locations.[70] The NCCN 2012 guidelines further specify that
cystoscopy and urinary cytology should be performed every 3-6 months for 2 years
and then at increasing intervals as appropriate.[42]

Keganasan buli merupakan 4-10% dari semua keganasan di USA (United States Of
America) dan menyebabkan sekitar 10.000 kematian per tahun. Pada 2005,
diperkirakan terdapat 63.210 kasus baru dengan lebih dari 13.000 kematian.
Kemungkinan kekambuhan/rekurensi antara 50-90%, tergantung pada
staging, grade, dan jumlah tumor primer. Progresi stage and grade terjadi
antara 10-50% kasus. Karena tidak ada metode tunggal yang 100% sensitif untuk
monitoring rekurensi pada penderita maka biasanya digunakan kombinasi beberapa
cara. Cara diagnosis utama pada keganasan buli adalah dengan flexible
cystoscopy, karena risiko tindakan rendah dan dapat dilakukan pada tempat
praktek dokter. Namun, jika ditemukan lesi datar seperti pada carcinoma in-situ sulit
untuk membedakan dengan buli normal. Oleh karena itu, flexible cystoscopy lebih
bermanfaat jika dipakai untuk diagnosis pada keganasan yang sudah nyata.
Sensitivitas uji ini sangat dipengaruhi oleh grade tumor. Pada high-grade tumors
dengan pleomorfisme yang jelas dan gambaran nukleus abnormal, akan dengan
mudah dideteksi secara akurat dengan flexible cystoscopy. Namun, jika small and/or
well differentiated tumors, di mana bedanya dengan normal sedikit, maka sukar
dideteksi dengan cystoscopy. Untuk kasus yang masih dini atau tumor dengan
diferensiasi baik, minimal dibutuhkan cara diagnosis lain seperti pemeriksaan marker urin. Misalnya nmp2, nmp 2, 9, fibronectin, cytokeratin 2,18,
bladder cancer specific protein blca-4, aktivitas telomerase, bladder associated
antigen (bta), urothelial carcinoma associated 1 (uca1), serta nmp22, dna ploidy &
s-phase fraction. 1-3,5-20 Selain cystoscopy, diagnosis dapat juga dilakukan dengan
upper tract imaging untuk mendeteksi tumor urotelial tambahan dan adanya
obstruksi saluran kemih.20
Daun sirsak diketahui sebagai bahan yang paling ampuh untuk mengobati kanker.
Salah satu penyebabnya karena daun sirsakmengandung senyawa annonaceous

acetogenins yang berkemampuan 10.000 kali lebih kuat dalam membunuh sel
kanker dibandingkan adriamycin (yang umum digunakan dalam kemoterapi).
Senyawa ini sangat selektif, hanya menempel pada sel-sel kanker dan merusak ATP
(sumber energi) pada dinding mitokondria, sehingga tidak ada energi yang tersisa
untuk mempertahankan hidup sel kanker.

Untuk memperoleh senyawa annonaceous acetogenins dapat dilakukan dengan

menyuling daun sirsak agar diperoleh minyaknya. Hal ini akan diperoleh senyawa
annonaceous acetogenins lebih banyak dari pada hanya sekedar mengkonsumsi
daun sirsak langsung.
Life Sci. 2006 Jan 18;78(8):869-74. Epub 2005 Sep 8.
Selective cytotoxicity of squamocin on T24 bladder cancer cells at the S-phase via a
Bax-, Bad-, and caspase-3-related pathways.
Yuan SS1, Chang HL, Chen HW, Kuo FC, Liaw CC, Su JH, Wu YC.
Annonaceous acetogenins are a group of potential anti-neoplastic agents isolated
from Annonaceae plants. We purified squamocin, a cytotoxic bis-tetrahydrofuran
acetogenin, from the seeds of Annona reticulata and analyzed its biologic effects on
cancer cells. We showed that squamocin was cytotoxic to all the cancer lines tested.
Furthermore, squamocin arrested T24 bladder cancer cells at the G1 phase and
caused a selective cytotoxicity on S-phase-enriched T24 cells. It induced the
expression of Bax and Bad pro-apoptotic genes, enhanced caspase-3 activity,
cleaved the functional protein of PARP and caused cell apoptosis. These results
suggest that squamocin is a potentially promising anticancer compound.

Prof Dr Drs Sukardiman, Spt.M.Sc, menciptakan kapsul "Androma" yang merupakan

obat antikanker dari bahan herbal (tanaman obat).
"Androma itu perpaduan dari kata-kata Latin untuk sambiloto dan kunyit, karena
ekstrak antikanker itu memang saya buat dari sambiloto dan kunyit," kata guru
besar Fakultas Farmasi (FF) Unair Surabaya

Mol Cancer Ther. 2007 Mar;6(3):1022-30.

Curcumin potentiates the apoptotic effects of chemotherapeutic agents and
cytokines through down-regulation of nuclear factor-kappaB and nuclear factorkappaB-regulated gene products in IFN-alpha-sensitive and IFN-alpha-resistant
human bladder cancer cells.

Kamat AM1, Sethi G, Aggarwal BB.

Whether curcumin, a yellow curry pigment commonly consumed in countries, such
as India, has any role in prevention or treatment of bladder cancer was investigated.
We found that curcumin inhibited the proliferation, induced cell cycle arrest, and
DNA fragmentation in both IFN-alpha-sensitive (RT4V6) and IFN-alpha-resistant (KU7) bladder cancer cells. Curcumin also potentiated the apoptotic effects of the
chemotherapeutic agents (gemcitabine and paclitaxel) and of cytokines [tumor
necrosis factor (TNF) and TNF-related apoptosis-inducing ligand]. This effect of
curcumin was independent of sensitivity and resistance to IFN-alpha, commonly
used for treatment of bladder cancer. Whether the effects of curcumin are mediated
through modulation of the nuclear factor-kappaB (NF-kappaB) pathway known to
mediate antiapoptosis was investigated. Both gemcitabine and TNF activated NFkappaB in bladder cancer cells and curcumin suppressed this activation. Similarly,
cigarette smoke, a major risk factor for bladder cancer, also activated NF-kappaB
and curcumin suppressed it. Cigarette smoke-induced expression of the NF-kappaBregulated gene products cyclooxygenase-2 and vascular endothelial growth factor,
linked with proliferation and angiogenesis, respectively, was also down-regulated by
curcumin
Anticancer Res. 2015 Feb;35(2):645-51.
Potential anticancer properties and mechanisms of action of curcumin.
The purpose of this review is to focus on the anti-tumor effects of curcumin.
Curcumin inhibits the STAT3 and NF-B signaling pathways, which play key-roles in
cancer development and progression. Also, inhibition of Sp-1 and its housekeeping
gene expressions may serve as an important hypothesis to prevent cancer
formation, migration, and invasion. Recent data have suggested that curcumin may
act by suppressing the Sp-1 activation and its downstream genes, including
ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in a concentration-dependent
manner in colorectal cancer cell lines; these results are consistent with other
studies, which have reported that curcumin could suppress the Sp-1 activity in
bladder cancer and could decrease DNA binding activity of Sp-1 in non-small cell
lung carcinoma cells. Recent data advocate that ER stress and autophagy may as
well play a role in the apoptosis process, which is induced by the curcumin analogue
B19 in an epithelial ovarian tumor cell line and that autophagy inhibition could
increase curcumin analogue-induced apoptosis by inducing severe ER stress. The
ability of curcumin to induce apoptosis in tumor cells and its anti-angiogenic
potential will be discussed in this review..
Anticancer Res. 2003 Jan-Feb;23(1A):363-98.
Anticancer potential of curcumin: preclinical and clinical studies.
Aggarwal BB1, Kumar A, Bharti AC.

Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma

longa, commonly called turmeric. Extensive research over the last 50 years has
indicated this polyphenol can both prevent and treat cancer. The anticancer
potential of curcumin stems from its ability to suppress proliferation of a wide
variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines,
cell surface adhesion molecules and cyclin D1; down-regulate growth factor
receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal
kinase, protein tyrosine kinases and protein serine/threonine kinases. In several
systems, curcumin has been described as a potent antioxidant and antiinflammatory agent. Evidence has also been presented to suggest that curcumin
can suppress tumor initiation, promotion and metastasis.

BJU Int. 2013 Dec;112(8):1073-9. doi: 10.1111/bju.12062.

Complementary and alternative medicine (CAM) in prostate and bladder
cancer.
Philippou Y, Hadjipavlou M, Khan S, Rane A.
To provide an overview of the scientific and clinical studies underlying the most
common vitamin and herbal preparations used in prostate and bladder cancer and
evaluate the evidence behind them. A literature search was undertaken on PubMed
using various keywords relating to the use of complementary and alternative
medicine (CAM) in prostate and bladder cancer.Vitamin E and selenium
supplementation can potentially have adverse effects by increasing the risk of
prostate cancer. Initial clinical studies of pomegranate and green tea, investigating
their chemotherapeutic properties in prostate and bladder cancer have yielded
encouraging results. Curcumin, resveratrol, and silibinin have potential anticancer
properties through multiple molecular targets; their clinical effectiveness in prostate
and bladder cancer is yet to be evaluated. Zyflamend, like PC-SPES, is a combined
CAM therapy used in prostate cancer. Acupuncture is popular among patients
experiencing hot flushes who are receiving androgen-deprivation therapy for
prostate cancer. Conclusive evidence for the use of CAM in prostate and bladder
cancer is lacking and not without risk.