A Clinical Study of Pelvic Concurrent Chemoradiotherapy Combined with CT-guided Intracavitary Brachytherapy with Adaptive Simultaneous Dose Escalation for Locally Advanced Cervical Cancer

The standard treatment for locally advanced cervical cancer is cisplatin-based concurrent chemoradiotherapy with external beam radiotherapy (EBRT) and Brachytherapy (BT). overall treatment time (OTT) has been found to be an important predictor of treatment response. Some studies have shown that the acceleration of tumor cell regeneration during the extension of radiotherapy leads to poor local control. Prolonging the overall treatment time of cervical cancer radiotherapy for more than 8 weeks leads to an increase in pelvic local control failure. Therefore, shortening OTT has great potential benefits from both clinical efficacy and social benefits. Shortening OTT in radical cervical cancer radiotherapy includes hypofractionated EBRT and shortening the interval between BT and EBRT. However, further shortening OTT may lead to an increase in acute and late toxicity. Adaptive radiotherapy (ART) strategies systematically monitor variations in target and neighbouring structures to inform treatment-plan modification during radiotherapy. The application of image-guided adaptive brachytherapy (IGABT) has clearly demonstrated the advantages of this approach in the treatment of cervical cancer. Previous studies have shown that the implementation of IGABT can achieve personalized treatment, dose increase, improve clinical efficacy, reduce normal tissue toxicity and side effects, and strengthen international standardized quality control. In this study, online adaptive pelvic EBRT combined with IGABT based on uRT-linac was performed under online CT guidance.
The aim of this study is to evaluate the safety and efficacy of pelvic concurrent chemoradiotherapy combined with CT-guided intracavitary brachytherapy with adaptive simultaneous dose escalation in locally advanced cervical cancer.

Start Date15 Mar 2025

Sponsor / Collaborator

Peking University Third Hospital

IRCT20241216064072N1

/ SuspendedPhase 3IIT

The Effect of S-Adenosyl-L-Methionine on Sexual Function in Individuals Receiving Methadone Maintenance Treatment: A Double-Blind, Placebo-Controlled Clinical Trial

Start Date29 Jan 2025

Sponsor / Collaborator-

CTR20244707

/ Active, not recruitingNot Applicable

丁二磺酸腺苷蛋氨酸肠溶片人体生物等效性试验

[Translation] Bioequivalence study of enteric-coated adenosylmethionine butanedisulfonate tablets in humans

在健康受试者体内，在空腹/餐后状态下，以ABBOTT LABORATORIES (M) SDN. BHD持证，ABBVIE S.R.L.生产的丁二磺酸腺苷蛋氨酸肠溶片（商品名：思美泰Transmetil；规格：0.5 g（以腺苷蛋氨酸计））为参比制剂，研究成都赛璟生物医药科技有限公司研制的丁二磺酸腺苷蛋氨酸肠溶片（受试制剂；规格：0.5 g（以腺苷蛋氨酸计））的吸收速度和吸收程度，评价受试制剂与参比制剂是否生物等效。观察受试制剂和参比制剂在中国健康受试者中的安全性。

[Translation]

In healthy subjects, under fasting/postprandial conditions, the absorption rate and extent of enteric-coated adenosylmethionine butanedisulfonate tablets (trade name: Transmetil; specification: 0.5 g (in terms of adenosylmethionine)) produced by Chengdu Saijing Biopharmaceutical Technology Co., Ltd. (test preparation; specification: 0.5 g (in terms of adenosylmethionine)) were studied using ABBOTT LABORATORIES (M) SDN. BHD as the reference preparation, and the bioequivalence of the test preparation and the reference preparation was evaluated. The safety of the test preparation and the reference preparation in healthy Chinese subjects was observed.

Start Date03 Jan 2025

Sponsor / Collaborator

Chengdu Saijing Biomedical Technology Co., Ltd.

100 Clinical Results associated with Ademetionine 1,4-Butanedisulfonate

100 Translational Medicine associated with Ademetionine 1,4-Butanedisulfonate

100 Patents (Medical) associated with Ademetionine 1,4-Butanedisulfonate

11,234

Literatures (Medical) associated with Ademetionine 1,4-Butanedisulfonate

01 May 2025·Journal of Molecular Graphics and Modelling

Elucidating the impact of S-adenosylmethionine and histamine binding on N-methyltransferase conformational dynamics: Insights from an in silico study

Article

Author: Li, Congcong ; Qu, Ge ; Sun, Zhoutong ; Sun, Shuyang ; Chu, Qi

S-adenosylmethionine (SAM)-dependent histamine N-methyltransferase (HNMT) is a crucial enzyme involved in histamine methylation, playing an important role in the epigenetic modification of biology. It entails the addition of methyl groups to histamine molecules, thereby regulating gene expression, cellular signal transduction, and other biological processes. Therefore, gaining a profound understanding of the detailed mechanism underlying HNMT-mediated methylation reactions is instrumental in elucidating the role of histamine methylation in biology. This study employed molecular dynamics (MD) simulations to assess the mechanism of cooperative catalytic reaction between the substrate-binding domain (S domain) and the cofactor-binding domain (C domain) of HNMT. The results indicated that the interplay between the cofactor (SAM) and the C domain was mostly unaltered by substrate Histamine (HSM) binding. Nevertheless, SAM binding could induce conformational changes in the S domain, thus creating a favorable environment for substrate recognition and catalysis. Additionally, key amino acid residues that significantly contributed to substrate binding were identified based on molecular mechanics-generalized Born surface area (MM/GBSA) calculations. These findings could serve as a theoretical basis for the design of potential inhibitors and modulators targeting HNMT.

01 Apr 2025·Food Chemistry

Non-targeted and targeted detection of hydrophilic compounds in fu brick tea: A study on samples from major Chinese production regions and different processing stages

Article

Author: Huang, Jianan ; Xu, Junren ; Yuan, Yong ; Yin, Feiyan ; Zhao, Mengmeng ; Li, Na ; Liu, Zhonghua ; Zhu, Mingzhi ; Zhao, Yiqiao ; Wang, Kunbo ; Chao, Jin

Systematic research is still lacking on the content of hydrophilic compounds in Fu Brick Tea (FBT) from major Chinese production regions and their variation patterns during the processing of FBT. This study utilized optimized non-targeted (UHPLC-Q-Exactive Orbitrap-MS) and targeted (UHPLC-QqQ-MS) metabolomics to analyze 73 FBT samples from six regions of China and 30 samples from different stages of FBT processing. 573 and 74 hydrophilic compounds were respectively relatively and absolutely quantified for the first time. Among the 73 FBT samples, alkaloids were the most abundant (26221.76-36701.75 mg/kg), followed by soluble sugars (211372.59-26112.85 mg/kg), organic acids (17014.07-23589.20 mg/kg), amino acids (6664.59-9791.46 mg/kg), nucleotides (1020.33-2175.16 mg/kg), and nucleoside (650.86-1446.26 mg/kg). During the processing of FBT, sugars, acids, nucleotides, and nucleosides increased, while amino acids decreased, and alkaloids slightly increased. This study enhances the understanding of hydrophilic compounds in FBT.

01 Apr 2025·Food Chemistry

Uncovering metabolite changes of potato Fusarium sambucinum infection based on a UPLC-Q-TOF metabonomic approach

Article

Author: Zhang, Fan ; Xie, Shiyuan ; Pan, Xinyue ; Wang, Wenxiu ; Shi, Qi ; Chen, Kexiang ; Sun, Jianfeng

Fusarium sambucinum causes dry rot disease and postharvest storage losses in potatoes. Understanding the defense mechanisms of potato plants may lead to the development of rational disease control approaches. In the present study, "Kexin one" potato variety was infected with F. sambucinum, and samples were collected at 0, 10, and 20 d post-infection and analyzed using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry to determine metabolic differences. We identified 1049 significant differential metabolites belonging to 12 categories, including organic and amino acids and peptides, which can be biomarkers for dry rot in potatoes following F. sambucinum infection. Physiological and biochemical indicators of dry rot potatoes were explored, and the results were consistent with those of metabolomic data. The findings of this study provide a basis for the control of dry rot and prevention of postharvest losses in potatoes.

News (Medical) associated with Ademetionine 1,4-Butanedisulfonate

21 Aug 2023

·synapse.patsnap.com

Progress in the Research and Development of METTL3 Drug Targets

METTL3 is an RNA methyltransferase that catalyzes the methylation of RNA at N6-adenosine, making it a key player in this process. Abnormal expression of METTL3 can lead to various diseases, including cancer, cardiovascular disorders, and neurodegenerative diseases. Therefore, finding inhibitors of METTL3 could help further our understanding of the biological functions of this enzyme and aid in the development of new treatments. N6-methyladenosine (m6A) is one of the most common and abundant covalent modifications in messenger RNA. First discovered in bacterial and eukaryotic RNA back in 1958, approximately 0.1% to 0.5% of mRNA adenines are modified by m6A. In vitro data suggests that m6A modifications affect fundamental biological processes of mRNA, including expression, splicing, localization, and translation. The occurrence of m6A modifications demonstrates tissue specificity, with significant variations observed between healthy and diseased tissues. Timeline of m6A Discovery The METTL3, an RNA methyltransferase, is one of the primary enzymes catalyzing m6A modification of RNA, but not the only one. It coexists with METTL14 and Wilms Tumor 1 Associated Protein (WTAP) in the form of a heterotrimeric complex. METTL3 possesses catalytic activity, transferring methyl groups from cofactor S-adenosylmethionine to substrate RNA, while METTL14 facilitates the binding of the substrate RNA. WTAP locates the complex at a specific nuclear region and positions the RNA substrate onto the complex. METTL3 plays roles in various aspects of cancer development. Knocking out the METTL3 gene in lung cancer cell lines and Hela cells results in decreased growth, survival, and invasion of human lung cancer cells. In human bladder, the expression of METTL3 is significantly upregulated, and the knockout of METTL3 significantly reduces the proliferation, invasion, in vitro survival, and in vivo tumorigenicity of bladder cancer cells. Competitive Landscape By entering "Mettl3" into the Synapse database, the clinically relevant molecule STC-15 can be found. In addition, a batch of molecules is in the preclinical research stage, including SAM binding pocket inhibitors, conformation inhibitors, natural products, and adenine analogs. According to a review summarized by Professor Qidong You in "Drug Discovery Today", the binding pattern of METTL3-METTL14 with inhibitors can be divided into three parts: part A is the aromatic ring, part B is the connecting chain, part C is the amino hydrophobic chain. Furthermore, the available cocrystal structures of METTL3-METTL14 and its inhibitors can help rationally design new molecules. To achieve this goal, analyzing the cocrystal structures of METTL3-METTL14 and conformation inhibitors will provide new ways for the development of new tools and potential drugs. Accent Therapeutics, which is in the same field, was established in 2017 and has attracted attention from several capitals, and has had strong development momentum in recent years. The company announced in April 2020 that it completed a $63 million B round of financing to advance new precise cancer treatments for RNA modification proteins (including METTL3 and ADAR1). At present, the company has received more than $100 million in financing. In June of the same year, Accent announced a partnership with pharmaceutical giant AstraZeneca. Key DrugSTM2457 is the first METTL3 class small molecule inhibitor developed by the UK pharmaceutical company STORM THERAPEUTICS. Unlike other RNA methyltransferases, STM2457 has high specificity for METTL3 (IC50=51.7 μM). It can induce apoptosis in cells of AML patients and mouse AML models, but it does not induce apoptosis in normal non-leukemic hematopoietic cells. After treatment, it can reduce the number of human CD45 cells in the bone marrow and spleen of mice. STORM THERAPEUTICS had raised £30 million in its Series A financing and began human clinical trials for the latest generation METTL3 inhibitor, STC-15, on November 15, 2022. The study's indication is for advanced solid tumors. This study is a phase I, multi-center, open-label study with a 3+3 cohort design, expecting to recruit 66 patients. The aim is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of STC-15 in multiple escalating daily oral doses in the Q3W treatment cycle, with dose levels determined by the modified Fibonacci algorithm. The study aims to systematically assess the safety, tolerance, pharmacokinetics, and pharmacodynamics of STC-15 in adult patients with advanced malignant tumors. The dose levels further evaluated in the expanded cohort will be selected based on available PK, pharmacodynamics, target activity, efficacy, safety, and tolerability data, including long-term safety data beyond Dose Limiting Toxicity (DLT). As METTL3 is a SAM-dependent methyltransferase, the earliest prototypes of METTL3 inhibitors were structural analogues of SAM. We are still in the early stage of discovering potent and selective METTL3 inhibitors, and many biological questions about the mechanism and function of the METTL3-METTL14 complex remain unanswered. STC-15 is the only drug that has entered the clinical stage. Interruption of METTL3-METTL14 activity could potentially lead to damage to fundamental physiological processes, resulting in harmful outcomes. To thoroughly validate METTL3-METTL14 as a manageable drug target, a multi-disciplinary approach is required to further elucidate its biological function in a broader context of epitranscriptomics.

03 Apr 2023

·www.pharmaceutical-technology.com

Eisai and National Cancer Center partner for tazemetostat clinical research

Tazemetostat received approval to treat relapsed or refractory EZH2 gene mutation-positive follicular lymphoma in Japan. Credit: Nephron/ commons.wikimedia.org. Eisai and the National Cancer Center have signed an agreement to partner on investigator-initiated clinical research for the anti-cancer agent, tazemetostat (Tazverik Tablets 200mg), based on the Patient-Proposed Healthcare Services system. Under this system, patients can request access to medical treatment using unapproved drugs not covered by insurance from the government. Treatment is then conducted as a clinical trial by the National Cancer Center Hospital to confirm its safety and efficacy. Eisai will be responsible for providing tazemetostat to the National Cancer Center Hospital free of charge. The drug will be utilised by the hospital in a clinical trial of tazemetostat for paediatric and AYA patients with malignant tumours that have no established standard of care, or which are refractory to the standard of care. The first-in-class, oral small molecule epigenetic enzyme EZH2 inhibitor tazemetostat was jointly researched and developed by Eisai and Epizyme . It inhibits EZH2 selectively with S-adenosylmethionine (a methyl group donor) for suppressing H3K27 methylation. Developed using Epizyme ’s proprietary product platform, tazemetostat received approval to treat relapsed or refractory EZH2 gene mutation-positive follicular lymphoma in Japan in 2021. The agent received accelerated approval in the US to treat metastatic or locally advanced epithelioid sarcoma in adults and paediatric patients aged 16 years and above, who are not eligible for complete resection, in January 2020. It also received accelerated approval for the treatment of relapsed or refractory follicular lymphoma in adult patients who had previously received at least two regimens of treatment, as well as those whose tumours are positive for an EZH2 mutation, when detected using a test approved by the FDA.

Drug ApprovalAccelerated ApprovalLicense out/inClinical Study

03 Apr 2023

·www.eisai.com

EISAI ENTERS INTO AGREEMENT WITH NATIONAL CANCER CENTER TO COLLABORATE ON INVESTIGATOR-INITIATED CLINICAL RESEARCH FOR ANTICANCER AGENT TAZEMETOSTAT BASED ON “PATIENT-PROPOSED HEALTHCARE SERVICES” SYSTEM

For Print（180KB） April 3, 2023 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has entered into an agreement with the National Cancer Center to collaborate on investigator-initiated clinical research for the EZH2 inhibitor tazemetostat hydrobromide (generic name, product name “Tazverik® Tablets 200 mg”, “tazemetostat”) based on “Patient-Proposed Healthcare Services” system. This clinical research will be conducted by the National Cancer Center Hospital. The “Patient-Proposed Healthcare Services” system is a system under which medical treatment using unapproved drugs not covered by insurance is applied for to the government based on the patient's request, and is conducted as a clinical trial to confirm safety and efficacy. Under the terms of the agreement, Eisai will provide tazemetostat free of charge to the National Cancer Center Hospital as the drug to be used in “A clinical trial of Tazemetostat for pediatric and AYA* patients with malignant tumors which have no standard of care or and which is refractory to standard of care: Patients-Proposed Healthcare Service” to be conducted by the hospital under this program. Researched and developed by Eisai and Epizyme, Inc.,** an Ipsen (Headquarters: France) company, tazemetostat is a first-in-class, oral small molecule inhibitor of the epigenetic enzyme EZH2. It is one of the histone methyltransferases in the epigenetics-related protein group, and is thought to regulate the expression of cancer-related genes and suppress the growth of cancer cells by specifically targeting EZH2, which contributes to the cancer growth process.1 Eisai holds the rights for development and commercialization of tazemetostat in Japan, where it was approved for the indication of “relapsed or refractory EZH2 gene mutation-positive follicular lymphoma (only when standard treatment is not applicable)” in 2021, and manufactures and distributes the product. Eisai positions oncology as a key franchise area and aims to create innovative drugs that act towards curing cancer. Eisai is committed to expanding the potential clinical benefits of tazemetostat for cancer treatment, as it seeks to contribute to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families and healthcare professionals. * AYA (Adolescent & Young Adult): Patients between the ages of 15 and 39. ** Acquired by Ipsen in 2022 Media Inquiries: Public Relations Department, Eisai Co., Ltd. +81-(0)3-3817-5120 [Notes to editors] 1. About the “Patient-Proposed Healthcare Services” system The “Patient-Proposed Healthcare Services” system is a system that allows patients who wish to use unapproved drugs and other medications as uninsured treatment to do so promptly, based on the patient's request, while confirming the safety and efficacy of the drug and allowing access to the unapproved drugs at medical institutions close by. The objective is to accumulate data and scientific evidence for future insurance coverage. Ministry of Health, Labour and Welfare “Patient-Proposed Healthcare Services” (Moushide Ryouyou) System: https://www.mhlw.go.jp/moushideryouyou/ (Japanese only) 2. About tazemetostat hydrobromide (generic name, product name “Tazverik® Tablets 200 mg”) Tazemetostat is a first-in-class, oral small molecule inhibitor that targets EZH2 that was jointly researched and developed under the alliance agreement between Eisai and Epizyme, Inc., an Ipsen company, utilizing Epizyme, Inc.'s proprietary product platform. This agent selectively inhibits EZH2 in a competitive matter with S-adenosylmethionine (a methyl group donor) to suppress methylation of H3K27.1 Eisai is responsible for development and commercialization of this agent in Japan, where the drug was approved in June 2021 for the indication of “relapsed or refractory EZH2 gene mutation-positive follicular lymphoma (only when standard treatment is not applicable)”. Ipsen is responsible for the development and commercialization of this agent in the United States, where accelerated approval was granted for in January 2020 with the indication of “adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection”. In June of the same year, the accelerated approval was granted for this agent with the indication of “adult relapsed / refractory follicular lymphoma who had at least 2 regimens of prior treatment and whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test”, and of “adult relapsed / refractory follicular lymphoma for which there are no satisfactory alternative treatment options”. This agent is not approved outside of Japan and the United States. 3. About epigenetics Epigenetics is a branch of science that studies the mechanism for the acquired activation/inactivation of gene function and seeks to determine how gene function is inherited through cell division, irrespective of DNA base sequence alteration. Examples of modification that lead to the regulation of gene expression include methylation of DNA and modifications of histone (methylation, acetylation, phosphorylation, etc.). 4. About EZH2 EZH2 is one of the histone methyltransferases within a larger class of epigenetics-related proteins, and specifically catalyzes the methylation of histone H3 at lysine 27 (H3K27), thus controlling expression of various genes. It is indicated that an increase in methylation of H3K27 caused by EZH2 gain-of-function mutation, overexpression, or the dysfunction of the SWI/SNF (switch/sucrose non-fermenting) complex that reportedly inhibits EZH2 methylation activity, plays an important role in carcinogenesis.1 1 Sarah K. Knutson, Satoshi Kawano, Yukinori Minoshima, et al. Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent Antitumor Activity in EZH2-Mutant Non-Hodgkin Lymphoma. Molecular Cancer Therapeutics. 2014 Apr; 13(4):842–854

License out/inDrug ApprovalAccelerated ApprovalClinical StudyAcquisition

100 Deals associated with Ademetionine 1,4-Butanedisulfonate

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KEGG	Wiki	ATC	Drug Bank
-	Ademetionine 1,4-Butanedisulfonate	A16AA02	DB00118

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Liver Cirrhosis, Biliary	China	Abbott Laboratories	02 Nov 2000
Cholestasis	Italy	Abbott Laboratories	01 Jan 1975

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
disorder of aging	Preclinical	China	Qingdao University	01 Mar 2024
Cholestasis, Intrahepatic	Preclinical	Russia	Alere, Inc.	01 Jun 2014
Nonalcoholic Steatohepatitis	Preclinical	Poland	Abbott Laboratories	01 Dec 2012
Nonalcoholic Steatohepatitis	Preclinical	Germany	Abbott Laboratories	01 Dec 2012
Nonalcoholic Steatohepatitis	Preclinical	Russia	Abbott Laboratories	01 Dec 2012
Nonalcoholic Steatohepatitis	Preclinical	France	Abbott Laboratories	01 Dec 2012
Depressive Disorder	Preclinical	United States	Meharry Medical College	13 Oct 2012
Liver Diseases, Alcoholic	Preclinical	United States	Abbott Laboratories	01 Sep 2005

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00513461 (CTgov)	Phase 2	Hepatocellular Carcinoma \| Hepatitis C	110	immunoenzyme technique+S-adenosyl-L-methionine disulfate p-toluene-sulfonate (Arm I (SAMe))	csbeocyxzr(ozdegfjorp) = imlcppzbgc zlchpezwne (xjttcdleul, szgbwupiru - xxjreblkte) View more	-	10 Aug 2018
				placebo (Arm II (Placebo))	csbeocyxzr(ozdegfjorp) = lemxikinjr zlchpezwne (xjttcdleul, ioeucvnpyq - faacjqwcze) View more
NCT00070941 (CTgov)	Phase 2/3	Depressive Disorder \| Parkinson Disease	29	SAM-e (SAM-e)	vfwmhnaqnh(jlkxrcpuix) = aqbccetwkz hudozzxpwa (zclngpsbnh, mpmclamftx - oosxtfzhbf) View more	-	13 Jul 2016
				oral escitalopram (Escitalopram)	vfwmhnaqnh(jlkxrcpuix) = mhdugghdju hudozzxpwa (zclngpsbnh, uddphkvnim - wgezycqswi) View more
AACR2014	Phase 2	Liver Cirrhosis	110	SAMe	(kwbxjpmfqu) = ijswmofmbg xsgjtuwqwn (kogpkdzzpy )	Negative	01 Oct 2014
				Placebo	(kwbxjpmfqu) = bkuxlnvfex xsgjtuwqwn (kogpkdzzpy )
NCT00762268 (CTgov)	Not Applicable	Bipolar Disorder	23	SAMe (SAMe)	tyedmdjhto(wgwkshygnf) = txrvtlecqk oqbimpaeij (nuslxpdysw, qfjwhjhzit - pqbowrubqn) View more	-	26 Aug 2014
				Placebo (Placebo)	tyedmdjhto(wgwkshygnf) = mwdfyecvrp oqbimpaeij (nuslxpdysw, pdmjxbbxin - huuwogxaqg) View more
NCT01140646 (SAMe, CTgov)	Phase 2	Hot Flashes	45	s-adenosyl-L-methionine	ouiipfaiky(gcakkeozfw) = adqwppfhup vpxtqxmaas (rlpckqzpax, dosoqscqwp - klvmlgftkz) View more	-	11 Apr 2014
NCT00694564 (CTgov)	Not Applicable	Abdominal Pain	8	S-adenosyl methionine (SAM-e)	(pvgnqacaex) = coyjjllnlo exqgjqlbxh (kgtydxpbgz, rxoeiwjuyg - mrdjrhquyl) View more	-	13 Sep 2013
				Sam-e (Sam-e (Treatment))	etlrsxdogj(imhkfkoqxk) = uheyqxvqww aposgvhwpk (dhpnbvgtsw, wnjyjvektv - txxeumzssf) View more
Tandem Meetings ASTCT and CIBMTR2012	Not Applicable	Posterior Leukoencephalopathy Syndrome tacrolimus	-	Tacrolimus held and restarted at same dose or lower therapeutic level	(ruaklgznme) = not clearly observed with PRES onset beafrtyqno (yjyinbztwz ) View more	Positive	01 Feb 2012
				Switched to another agent at time of PRES
NCT00722124 (CTgov)	Phase 2/3	Acral Lentiginous Malignant Melanoma	150	S-Adenosyl-L-Methionine (SAMe 800)	gowgcrmgag(ssczoczqai) = usryscmulk cezsolokzd (glveztwbpg, zldxeeebqa - axfpiiizhh) View more	-	09 Sep 2011
				S-Adenosyl-L-Methionine (SAMe 1600)	gowgcrmgag(ssczoczqai) = engqhzlexy cezsolokzd (glveztwbpg, bxltvafwsv - kptuwmkpuv) View more
IAS2010	Not Applicable	HIV Infections	37	Switch to RAL	slkbidnulh(pclwunuklp) = llyfzbajdb ccltjdzdtp (espcqixszc )	-	01 Jan 2010
				Maintain same regimen (control)	slkbidnulh(pclwunuklp) = cdsqezgxdu ccltjdzdtp (espcqixszc )
Studio Terapia Adiuvante Retto (STAR)-01 (ASCO2009)	Phase 3	Rectal Cancer	747	Infused FU concomitant to external-beam pelvic radiation	tukriikohk(wynktrzfhe) = mqixwrgjex xahgfxncrc (qkfxjhtnyy )	-	20 Jun 2009
				Same regimen + weekly OXA	escftesjfd(luwfpbgnpx) = wtiyveaorr rzgccxeghf (xqswjwfqiw ) View more

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Ademetionine 1,4-Butanedisulfonate

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