Micronutrients

Hematinics

All Drugs and Chemicals

Nootropic Agents

Gastrointestinal Agents

Lipid Regulating Agents

Vitamins

Folic Acid

Vitamin B Complex

Choline

Folinic Acid

Folate

Vitamin B9

Supply nutrition counseling and multivitamin supplement to people with poor nutritional status

Pregnancy diet (include one-carbon nutrients)

nutrition counseling

multivitamin supplement

Chien-Nan Lee

Kuang-Ta Huang

Chin-Pao Cheng

Rwei-Fen S. Huang

Parental one-carbon nutrient intake (folic acid and choline) and the genetic polymorphisms of one-carbon metabolic enzyme were interact with regulating embryonic one-carbon metabolic environment, affect fetal DNA and RNA biosynthesis and methyl modification of the genome molecule, to promote the individual nutrient growth factor of growth and development. Inadequate maternal one-carbon nutrient intake combined with genetic polymorphisms of one-carbon enzymatic mutation, causing one-carbon malnutrition, change fetal methyl metabolic nutrition environment. It not only leads to fetal growth mutation - such as folate and choline deficiency, increasing the risk of fetal neural tube defect but also induce abnormal modifying of fetuses's post-genomic methylation markers, may alter imprinted genes function of progenitors, recompile threshold sensitivity or domain in regulation of metabolic reactions of offspring, resulting in long-lasting effect, increasing the risk of chronic diseases of offspring such as cancer. According to the National Nutrition Survey results show that a considerable proportion of the Taiwanese people had poor one-carbon nutritional status. 48% of women intake 66% below the recommended intake reference value of folate. Whether inadequate parental one-carbon nutrients intake combined with genetic polymorphisms of one-carbon enzymatic mutation will cause one-carbon malnutrition of fetus, affecting fetal growth and modifying the risk of cancer development relationship of offspring. It is due to the lack of local ethnic data and empirical scientific reference at home and abroad, so it can not plan an effective maternal and children nutrient education and prevention strategies about methyl nutrition for early cancer prevention for Taiwanese. Therefore, indigenous people is the intended population of study in this project, screening of healthy pregnant women with high risk factor for cancer and obese pregnant women, and detection of one-carbon nutrient intake and biochemical assessment of the nutritional status of the study group. Supplying nutrition education intervention or multivitamin supplement to improve the poor nutritional status of persons. Using related DNA methylation imprint marker about offspring growth and modifying development of cancer as assessment, this project explores the appropriate one-carbon nutrient intake in parents and children and the assessments in regulation of growth and reducing the cancer-related risk.

Parental One-carbon Folate and Choline Nutrition Modulates Risk of Off-spring Cancer Development: Human Cohort Study

Using semiquantitative food frequency questionnaires (FFQ) to calculate dietary intake of one-carbon nutrient

Using 24 hours dietary recall and dietary record to calculate dietary intake of one-carbon nutrient

National Taiwan University Hospital

Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Fluorodeoxyglucose F18

Liver Extracts

Hypolipidemic Agents

Antimetabolites

Prospective inclusion of patients who are candidates for a transplant for CHC at the University Hospital of Lille and Rouen whose transplant project has been validated with a AFP score ≤ 2.

The systematic performance of a PET-CT with FDG and a PET-CT with Choline in all patients. At the end of the entire assessment, the patients will be (or not) registered on the transplant list and, for the patients registered on the list, a follow-up will be carried out at the level of a specialized transplant consultation every 3 months at during which the alphafoetoprotein dosage and abdominal imaging will be updated, until liver transplantation.

Performing an FDG TDM PET and a Choline TDM PET at two different times

PET TDM FDG-Choline

Guillaume Lassailly, MD

HCC is the most common malignant liver tumor for which liver transplantation is one of the pivotal curative treatments. The best possible selection of patients who are candidates for transplantation is essential in the current context of a shortage of transplants. Performing a PET CT scan is not currently recommended in the pre-liver transplant workup for HCC. However, PET CT using in a complementary manner the FDG and Choline tracers appears promising in the management of HCC in view of its wide use in oncology and its major diagnostic and prognostic contribution compared to conventional imaging. In order to address this issue, a prospective cohort study including patients from the University Hospital of Rouen and Lille with hepatocellular carcinoma meeting the criteria for indication of liver transplantation validated in SPC will be set up, the main objective of which will be to assess the decision-making contribution of PET TDM FDG and Choline in addition to conventional imaging in the pre-transplant assessment.

PET TDM FDG-Choline as a Decision-making Tool for Routine Care on the Liver Transplant List for HCC

Evaluation of PET TDM FDG-Choline as a Decision-making Tool for Routine Care on Inclusion on the Liver Transplant List for Hepatocellular Carcinoma

Composite endpoint corresponding to the rate of patients reclassified for lymph node fixation (N +) and / or extrahepatic extension (M +) after PET TDM FDG-Choline with a negative standard assessment (thoracic CT, abdominal imaging by CT or MRI) or patient not included on the list due to locally advanced disease not compatible with the graft (AFP score ≥ 3 or infiltrating HCC) not identified by the standard assessment.

Presence/absence of a double fixation TEP FDG and TEP Choline B. Presence of a single TEP FDG or Choline binding C. No FDG-Choline binding.

University Hospital, Lille

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Patients with prostate carcinoma confirmed by needle biopsy, age \>50 years, planned radical prostatectomy with lymph-node dissection, fasting for \>12 hours before FEC-PET and an interval between biopsy and PET \>3 weeks.

PET scans were performed on a LSO scanner (ECAT ACCEL, Siemens, Erlangen, Germany) by using a multiphase protocol starting with a "cold" transmission scan of the lower pelvis. This was followed by a list mode emission scan with 10 frames à 1 minute starting immediately after the administration of 3.3MBq \[18F\]Fluoroethylcholine chloride (FEC; Eckert \& Ziegler EURO-PET Berlin GmbH) as a bolus through the cubital vein. After a short gap due to computer processing time the whole body scan was performed starting at the upper thoracic aperture down to the proximal femur. Acquisition parameters were 3 minutes emission scan and 2 minutes transmission scan for each bed position. Therefore the prostate region was scanned again at 45 minutes p.i. (post injection) A delayed local acquisition at 65 minutes over the lower pelvis with 6 minutes emission and 2 minutes transmission finished the diagnostic acquisition procedure.

18F-Ethylcholine Positron Emission Tomography (FEC-PET)

The MRI examination was performed on a 1.5Tesla MRI system (Gyroscan ACS-NT, Philips, Hamburg, Germany) with combined QBody and endorectal coil. Pelvic assessment and lymph node staging was effected with 5mm T2 weighted (T2w) turbo spin echo (TSE) transversal and a coronal short-tau inversion recovery (STIR) sequence. For prostate assessment, 3mm endorectal T2w spin echo (SE) sagittal, transversal and coronal sequences were acquired.

Endorectal Magnetic Resonance Imaging (1.5Tesla) (eMRI)

Markus Hartenbach, Dr.

Christoph Sparwasser, Prof. Dr.

To investigate the sensitivity of the \[18F\]fluoroethylcholine (FEC) Positron-Emission-Tomography/ Magnetic Resonance Imaging (PET/MRI) method in tumour detection and location (side assignment, encapsulation, invasion of the seminal vesicle) and detection of affected lymph nodes, and to compare these with presently used detection procedures (needle biopsy, digital rectal examination, transrectal ultrasound, and pre-therapeutic assessment), with a view to finding out whether the \[18F\]fluoroethylcholine PET/MRI method is comparable to, or superior to, the established method. Postoperative histology served as the standard of reference.

Prostate carcinoma is today in Germany the most frequently diagnosed cancer disease of men and is - after bronchial carcinoma - their second most frequent cause of cancer-related death. Around 22% of all new cancer diagnoses among males are prostate-related. This corresponds to an age-adjusted incidence rate of nearly 100 per 100,000 males in the population, and to well above 40,000 new diagnoses of prostate cancer per year \[Robert-Koch-Institut, 2010\]. The dramatic increase in recent decades is attributable more to improved diagnostic methods and a generally increased life expectancy than to an actual increase in the incidence of disease \[Robert-Koch-Institut, 2010\].

The total annual mortality rate is around 11,000 \[Statistisches Bundesamt, 1994\]. Prostate carcinoma is virtually unknown among men under 40 years of age. The annual prevalence rises with increasing age - between the 40th and 80th years of life by a factor of more than 1000. Autopsies have shown that among men over 70 up to 80% have a latent prostate carcinoma, without it being fatal \[Breslow 1977; Börgemann, 2006\]. The patients' average age at diagnosis is 71 years.

The five-year prostate-cancer-specific survival rate after diagnosis is about 80-99% for tumours that are restricted to the gland itself \[Porter, 2006\]. For disseminated tumours this figure is considerably smaller, not more than 35% \[von Eschenbach, 1996\]. A prospect of complete regression exists only for non-metastasing carcinomas, but there it is quite good: under aggressive treatment, 90% of cancers restricted to the prostate itself can be completely cured, as can 50% of those that have crossed the gland's capsule \[Deutsche Gesellschaft für Urologie, 2009\].

At present, there is a lack of adequate pre-therapeutic staging methods. This in turn often prevents the reliable choice of a stage-adapted therapeutic regimen, which could possibly offer a better prognosis even for carcinomas extending into neighbouring organs. A consequence of this uncertainty is that in individual cases the therapy is not ideally suited to the stage of disease, and the success of radiation treatment, hormonal therapy and chemotherapy can only approximately be matched with the stage of dissemination. Until now, the only reliable method for lymph-node diagnosis is operative staging by lymphadenectomy. No reliable diagnostic method is available by which the degree of spreading of the tumour within the prostate can be established.

In this context, Positron-Emission-Tomography (PET) examination with radioactively labelled choline appears to offer a promising primary imaging-diagnostic staging method, as indicated by the studies reviewed below. This diagnostic method as applied to humans was first described by Gauthier et al. \[1985\]. This was followed by two detailed reports from a Japanese group: Hara et al. \[1997\] first investigated the potential of \[11C\]choline in brain tumours and found a clear enrichment of this marker in the tumours of 24 patients, while normal brain tissue was not enriched with it. In a subsequent study by the same group \[Hara, 1998\], the enrichment of fluorodeoxyglucose was compared with the choline uptake in the lesions of ten prostate-cancer patients. Thus, the choline enrichment (SUV, standardised uptake value) was 3.48 ± 1.31 in 43 lesions, while in the normal environment of the lesser pelvis the corresponding value was below 1.0. De Jong et al. \[2003\] investigated 67 patients, of whom 15 had histologically confirmed lymph-node metastases: the \[11C\]choline test gave a 'true positive' result in 12 of 15 patients and a 'false negative' in 3 patients, thus indicating that \[11C\]choline PET is sufficiently sensitive and specific for the pre-operative staging of lymph-node metastases of prostate carcinoma. In a pre-operative staging using Magnetic Resonance Imaging (MRI) with a combined endorectal and body-phased-array coil, Pegios et al. \[2003\] investigated 42 patients with strong clinical suspicion, or with needle-biopsy confirmation, of prostate cancer and were able to differentiate between stages of extracapsular growth and seminal-vesicle infiltration (tumor stage T2 versus T3 \[T2=tumor restricted to the gland itself; T3a=extracapsule growing of the tumor; T3b= tumor infiltration into the seminal-vesicles\]) with an accuracy of 94-97% (sensitivity 100%, specificity between 87% and 93% for observers 1 and 2). The exact, local tumour stage was identified with an accuracy of 75%. However, for lymph-node infiltration a sensitivity of only 25% was achieved: one of four lymph-node-positive patients was correctly identified. In a more recent study, a Japanese group \[Yamaguchi, 2005\] investigated the application of nuclear magnetic resonance (NMR) spectroscopy, magnetic resonance imaging (MRI) and choline-PET in 20 patients with needle-biopsy-confirmed prostate cancer. The PET imaging achieved a sensitivity of 100%, NMR (quotient \[(creatine + choline) / citrate\]) 65% and unsupported MRI 60%. For 16 patients radical prostatectomy was performed; results correlated with those of pre-operative local staging with PET by 81%, and with MRI by 50%. The site of choline uptakes in PET was visualised by MRI using the distance of the prostate from the femoral head and the pubic symphysis.At present, no data relevant for the present study indication are available on the software-fused imaging by combined PET/MRI. The combination of high-resolution endorectal MRI with functional PET imaging could come to offer a decisive advantage in the staging of prostate carcinoma. The present study was designed to test this in an appropriate patient population.

A system combining PET and MRI was recently granted approval in the U.S.A. by the U.S. Food and Drug Administration \[FDA, 2011\].

Clinical Value of FEC-PET Combined With Endorectal MRI for Pre-therapeutic Staging of Prostate Cancer

Clinical Value of [18]Fluoroethylcholine Positron-Emission-Tomography Combined With Endorectal Magnetic Resonance Imaging by Software Fusion for Pre-therapeutic Staging of Prostate Cancer

PET positive lesions were measured on its own and evaluated as malignant just as hypointense lesions on MRI. In PET/MRI analysis, MRI suspect lesions without FEC uptake were considered not to be malignant. PET positive lesions in central periurethral zone with inhomogenous signal intensity and sharp edges on MRI images were also considered to be benign. PET positive lesions in the peripheral zone without a hypointense correlate on MRI were considered to be malignant. At least 1 histological confirmed cancer lesion has to be detected by each of the 3 methods to be patient based true positive.

PET positive lesions (n=128) were measured on its own and evaluated as malignant just as hypointense lesions on MRI. In PET/MRI analysis, MRI suspect lesions without FEC uptake were considered not to be malignant. PET positive lesions in central periurethral zone with inhomogenous signal intensity and sharp edges on MRI images were also considered to be benign. PET positive lesions in the peripheral zone without a hypointense correlate on MRI were considered to be malignant. Sensitivity, specificity, accuracy, negative and positive predictive values were determined.

PET positive lesions in patients with Gleason \>6(3+3),n=43 were measured on its own and evaluated as malignant just as hypointense lesions on MRI. In PET/MRI analysis, MRI suspect lesions without FEC uptake were considered not to be malignant. PET positive lesions in central periurethral zone with inhomogenous signal intensity and sharp edges on MRI images were also considered to be benign. PET positive lesions in the peripheral zone without a hypointense correlate on MRI were considered to be malignant. Sensitivity, specificity, accuracy, negative \& positive predictive values were determined.

PET positive lesions were measured on its own and evaluated as malignant just as hypointense lesions on MRI. In PET/MRI analysis, MRI suspect lesions without FEC uptake were considered not to be malignant. PET positive lesions in central periurethral zone with inhomogenous signal intensity and sharp edges on MRI images were also considered to be benign. PET positive lesions in the peripheral zone without a hypointense correlate on MRI were considered to be malignant. Sensitivity, specificity, accuracy, negative and positive predictive values were determined without malign lesions \<=5mm.

Dr. Markus Hartenbach

Major Medical Corps and assistant medical director of the nuclear medicine department

The day before surgery, fasting patients received a bladder catheter right before Positron-Emission-Tomography/ Magnetic Resonance Imaging (PET/MRI) examination to avoid different sizes of the urinary bladder in PET and MRI scan and to reduce bladder FEC-activity overlay of the prostate. After applying the endorectal MRI coil patients were positioned in a vacuum mattress on MRI table. Additionally, 4 PET/MRI multimodality spot markers containing 37kBq \[22Na\] and a MRI T2w (T2 weighed) hyperintense gel were attached at the hip region to allow landmark PET/MRI fusion. After MRI acquisition the modular MRI table was fixed on the PET table system. Patients kept in the same position during the whole procedure. PET scans were performed by using a multiphase protocol starting with a list mode emission scan immediately after the administration of 3.3MBq \[18F\]fluoroethylcholine (FEC) as a bolus through the cubital vein.

FEC-PET/eMRI

Age, Categorical

Age Continuous

Sex: Female, Male

Germany

Region of Enrollment

Major Medical Corps Dr. Markus Hartenbach

results from FEC-PET as compared with histological results on a patient based analysis

Null hypothesis: patient distribution in contingency table is incidental.

results from MRI as compared with histological results on a patient based analysis

Null hypothesis: patient distribution in contingency table is incidental.

results from PET/MRI as compared with histological results on a patient based analysis

Null hypothesis: patient distribution in contingency table is incidental.

True Positive

False Positive

True Negative

False Negative

Total True

Total False

PET scans were performed on a LSO scanner (ECAT ACCEL, Siemens, Erlangen, Germany) by using a multiphase protocol starting with a "cold" transmission scan of the lower pelvis. This was followed by a list mode emission scan with 10 frames à 1 minute starting immediately after the administration of 3.3MBq \[18F\]Fluoroethylcholine chloride (FEC; Eckert \& Ziegler EURO-PET Berlin GmbH) as a bolus through the cubital vein. Acquisition parameters were 3 minutes emission scan and 2 minutes transmission scan for each bed position. Therefore the prostate region was scanned again at 45 minutes p.i. (post injection) A delayed local acquisition at 65 minutes over the lower pelvis with 6 minutes emission and 2 minutes transmission finished the diagnostic acquisition procedure.

[18F]Fluoroethylcholine Positron-Emission-Tomography (FEC-PET)

The MRI examination was performed on a 1.5Tesla MRI system (Gyroscan ACS-NT, Philips, Hamburg, Germany) with combined QBody and endorectal coil. Pelvic assessment and lymph node staging was effected with 5mm T2 weighted (T2w) turbo spin echo (TSE) transversal and a coronal short-tau inversion recovery (STIR) sequence. For prostate assessment, 3mm endorectal T2 weighed (T2w) spin echo (SE) sagittal, transversal and coronal sequences were acquired. Transversal sequences were angulated 90° to intraprostatic bladder catheter to allow exact correlation with histological holoptical slices.

Magnetic Resonance Imaging (MRI)

PET images at 45 min p.i. (post injection) and 65 min p.i. were fused with transversal endorectal and QBody T2 weighed (T2w) MRI images by using Hermes Medical Solutions Multi Modality landmark fusion tool. The four PET/MRI spot markers served as references. Without any patient movement between both modalities the fused images fitted exactly.

PositronEmissionTomography/MagneticResonanceImaging (PET/MRI)

Comparison of imaging results (FEC-PET, MRI and PET/MRI) with postoperative histological findings (all patients).

Number of Participants With Positive or Negative Results in PET, MRI or PET/MRI for Prostate Cancer Compared to Histological Findings

lesion based (all lesions = 128) results from FEC-PET as compared with histological results on a lesion based analysis of all patients (38)

Null hypothesis: patient distribution in contingency table is incidental.

lesion based (all lesions = 128) results from MRI as compared with histological results on a lesion based analysis of all patients (38)

Null hypothesis: patient distribution in contingency table is incidental.

lesion based (all lesions = 128) results from PET/MRI as compared with histological results on a lesion based analysis of all patients (38)

Null hypothesis: patient distribution in contingency table is incidental.

True positive

False positive

True negative

False negative

Total true

Total false

FEC-PET

The MRI examination was performed on a 1.5Tesla MRI system (Gyroscan ACS-NT, Philips, Hamburg, Germany) with combined QBody and endorectal coil. Pelvic assessment and lymph node staging was effected with 5mm T2w TSE transversal and a coronal STIR sequence. For prostate assessment, 3mm endorectal T2w SE sagittal, transversal and coronal sequences were acquired. Transversal sequences were angulated 90° to intraprostatic bladder catheter to allow exact correlation with histological holoptical slices.

PET images at 45 min p.i. and 65 min p.i. (post injection) were fused with transversal endorectal and QBody T2w MRI images by using Hermes Medical Solutions Multi Modality landmark fusion tool. The four PET/MRI spot markers served as references. Without any patient movement between both modalities the fused images fitted exactly.

PET/MRI

Comparison of lesion based (128)imaging results (FEC-PET, MRI and PET/MRI) with postoperative histological findings (all patients = 38).

Lesion Based Analysis of FEC-PET, Endorectal MRI and Combined FEC-PET/eMRI in All Patients

Lesion based analysis of FEC-PET, endorectal MRI and combined FEC-PET/eMRI in patients with Gleason Score \>6 (n=43) as compared with histological results on a lesion based analysis of all patients (38)

Null hypothesis: patient distribution in contingency table is incidental.

Lesion based analysis of FEC-PET, endorectal MRI and combined FEC-PET/eMRI in patients with Gleason Score \>6 (n=43) as compared with histological results on a lesion based analysis of all patients (n=38)

Null hypothesis: patient distribution in contingency table is incidental.

lesion based (patients with Gleasons Score \>6(3+3),n= 43) results from FEC-PET as compared with histological results on a lesion based analysis of all patients (38).

Gleason Grades: 1+2=well differentiated (rare), 3=moderately diff., 4=poorly diff., 5=undifferentiated

Gleason Score = histological primary grade + secondary grade (min=2,max=10)

Lesion Based Analysis of FEC-PET, Endorectal MRI and Combined FEC-PET/eMRI in Patients With Gleason Score >6 (3+3)

Lesion based analysis of FEC-PET, endorectal MRI and combined FEC-PET/eMRI in patients with malign lesions \>5mm (n=98) as compared with histological results on a lesion based analysis of all patients (n=38)

Null hypothesis: patient distribution in contingency table is incidental.

lesion based (malignant lesions \>5mm, n=98) results from FEC-PET as compared with histological results on a lesion based analysis of all patients (38)

Lesion Based Analysis of FEC-PET, Endorectal MRI and Combined FEC-PET/eMRI in Patients With Malignant Lesions >5mm (n=98)

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Nutritional and Metabolic Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Malnutrition

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Nutrition Disorders

Carcinoma, Bronchogenic

Bronchial Neoplasms

Vitamin B 12

Hydroxocobalamin

Vitamin B12

Cobalamin

Cyanocobalamin

Using to analysis metabolomic markers, one carbon folate nutrition levels in lung cancer patients.

Using to analysis folate, B12, homocysteine levels in plasma and RBC. Using to analysis cDNA gene test in buffy coat.

nutrition consult

Jin-Shing Chen

Rwei-Fen S.Huang

Non-small cell lung cancer (NSCLC) accounts for more than two-thirds of lung cancer, which is the leading cause of cancer deaths in Taiwan. The overall prognosis of NSCLC is poor with low 5-year survival rates. Recent advances suggest that malignancy NSCLC cancers are the cancer stem cell (CSC) diseases. The stemness potentials of CSC with epithelial-mesenchymal transdifferentiation ensure their invasion and disseminate to metastsis organs. The self-renewal property of CSC mediates intrinsic drug resistance to cytotoxicity therapy and promoted aggressive relapse tumour. Metabolic reprogramming on bioenergetics of malignant cancer cells has been proposed as the key mediator in the stemness CSC development. Malignancy cells uptake glucose for fermented glycolysis to produce lactate which release resulted in acidified microenvironment to trigger the mTOR and sonic hedgehog metabolic stress signaling in supporting CSC stemness potentials. The metabostemness of cancer cells is the new-dimensional hallmark of malignancy tumour, which may serve as the diagnostic markers for the early detection of malignancy cancers. Folate-mediated one carbon metabolism coordinates glucose into amino acid metabolism to tailor the fuel metabolites in supporting macromolecule synthesis and to sustain the bioenergetics requirement. Acting as the metabolic stressor, low folate intake is associated with increased risks of lung cancers. Folate and one-carbon nutrient status of NSCLC patients in Taiwan, however, has not been assessed. The role of low folate metabolic stress (LFMS) in metabostemness marker and metastasis potentials of malignancy NSCLC is unexplored. The causal effect and the working mechanisms by which LFMS promoted NSCLC malignancy remain elusive.

blood sample 10c.c

lung tumor tissue

non-lung tumor tissue

Folate One-carbon Malnutrition as the Metabostemness Risk Factor of Malignancy Tumor Development of NSCLC Patients

Folate One-carbon Malnutrition as the Metabostemness Risk Factor of Malignancy Tumor Development and the Prognostic Predictor of Non-small Cell Lung Cancer Patients

Using semiquantitative food frequency questionnaires

Using blood analysis to calculate the levels of one carbon nutrition

Using LC/MS or GC/MS to claculate metabolomic markers

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Nervous System Diseases

Breast Neoplasms

Melanoma

Neoplasm Metastasis

Brain Neoplasms

Skin Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Breast Diseases

Steinar Lundgren, MD PhD

The aim of the study is to investigate the feasibility of in vivo single volume MR spectroscopy in evaluation of treatment response in patients with brain metastases, using 3T MR instrument. In order to optimize and avoid ineffective treatment of patients with brain metastases, in vivo MR spectroscopy can be an useful tool.

Proton MR Spectroscopy of Brain Metastases in Evaluation of Treatment Response.

Single Volume 1H MR Spectroscopy of Brain Metastases in Evaluation of Treatment Response.

The Royal Norwegian Ministry of Health

Norwegian University of Science and Technology

Triple Negative Breast Neoplasms

Anti-Infective Agents

Anti-Allergic Agents

Anti-Inflammatory Agents

Respiratory System Agents

Antibodies

Immunomodulating Agents

Immunoglobulins

Efavirenz

Cromolyn Sodium

Immunologic Factors

Reverse Transcriptase Inhibitors

Enzyme Inhibitors

Antiviral Agents

Cytochrome P-450 Enzyme Inhibitors

Anti-Asthmatic Agents

Sodium cromoglicate with anti-PD-1 immunotherapy

PD-1 antibody SHR1210 200mg q2w chemotherapy (whether and which should be given depends on the treatment regimen before enrollment)

anti-PD-1 antibody and chemotherapy

Sodium Cromoglicate will be administered intranasally (nasal spray) (5 spray each nostril 4 times a day, 1 mg/spray)

Sodium Cromoglicate

Zhimin Shao, Professor

Zhonghua Wang, Professor

Yin Liu, Doctor

This is a Phase II, open-label, three-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, or efavirenz) with immune checkpoint inhibitor in mTNBC (triple negative breast cancer) patients who progressed during previous immune checkpoint inhibitors.

This is a Phase II, open-label, three-arm parallel study evaluating the efficacy and safety of combined treatment (sodium cromoglicate, choline, or efavirenz) with immune checkpoint inhibitors in metastatic TNBC (triple negative breast cancer) patients who progressed during or following previous immune checkpoint inhibitors. The investigators have achieved a breakthrough in the FUTURE study with an ORR (objective response rate) reaching 52.6% in IM (immunomodulatory) subtype TNBC patients. Despite this, there are still some IM subtype patients resistant to immunotherapy. How to reverse immunotherapy resistance or how to increase the sensitivity of immunotherapy efficacy, has become an urgent clinical problem to be solved. The preclinical results of our center show that TMAO, choline, and efavirenz play a potentially important role in regulating the tumor immune microenvironment. Oral choline can improve TMAO content in mouse serum, play the role of activating anti-tumor immunity, and improve immunotherapy efficacy. Preclinical studies of our center also show that sodium cromoglicate can enhance the anti-tumor immune response by inhibiting the activation of mast cells, increase the infiltration and function of cytotoxic CD8+ T cells, inhibit the growth of tumors in mice, and enhance the efficacy of PD-1 inhibitors in mice. Furthermore, another preclinical study of our center shows that efavirenz can enhance the anti-tumor immune response by inhibiting the retrotransposon of LINE-1 and decreasing intratumor heterogeneity. The combination of efavirenz and PD-1 inhibitors effectively inhibits tumor growth in mice. Based on preclinical studies, the investigators designed this study to enroll mTNBC patients who have progressed during or following immunotherapy, and to explore the efficacy of sodium cromoglicate, choline, or efavirenz combined with immunotherapy at a clinical level, providing new strategies of combined treatment for TNBC patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Parental One-carbon Folate and Choline Nutrition Modulates Risk of Off-spring Cancer Development: Human Cohort Study	NCT02266641	Off-spring Canc...	nutrition couns... multivitamin su...	21 Years - 40 Years	National Taiwan University Hospital
PET TDM FDG-Choline as a Decision-making Tool for Routine Care on the Liver Transplant List for HCC	NCT04792801	Hepatocellular ... Liver Transplan...	PET TDM FDG-Cho...	18 Years -	University Hospital, Lille
Clinical Value of FEC-PET Combined With Endorectal MRI for Pre-therapeutic Staging of Prostate Cancer	NCT00520546	Prostate Cancer	18F-Ethylcholin... Endorectal Magn...	50 Years -	German Federal Armed Forces
Folate One-carbon Malnutrition as the Metabostemness Risk Factor of Malignancy Tumor Development of NSCLC Patients	NCT03504098	Lung Cancer, No...	nutrition consu...	20 Years - 90 Years	National Taiwan University Hospital
Proton MR Spectroscopy of Brain Metastases in Evaluation of Treatment Response.	NCT00184288	Neoplasm Metast... Lung Neoplasms Breast Neoplasm... Melanoma		18 Years -	Norwegian University of Science and Technology
Folate One-carbon Malnutrition as the Metabostemness Risk Factor of Malignancy Tumor Development of NSCLC Patients	NCT03504098	Lung Cancer, No...	nutrition consu...	20 Years - 90 Years	National Taiwan University Hospital
Clinical Value of FEC-PET Combined With Endorectal MRI for Pre-therapeutic Staging of Prostate Cancer	NCT00520546	Prostate Cancer	18F-Ethylcholin... Endorectal Magn...	50 Years -	German Federal Armed Forces
PET TDM FDG-Choline as a Decision-making Tool for Routine Care on the Liver Transplant List for HCC	NCT04792801	Hepatocellular ... Liver Transplan...	PET TDM FDG-Cho...	18 Years -	University Hospital, Lille
Reverse Triple Negative Immune Resistant Breast Cancer	NCT05076682	Triple-negative...	Choline anti-PD-1 antib... Sodium Cromogli... Efavirenz	18 Years - 70 Years	Fudan University
PET TDM FDG-Choline as a Decision-making Tool for Routine Care on the Liver Transplant List for HCC	NCT04792801	Hepatocellular ... Liver Transplan...	PET TDM FDG-Cho...	18 Years -	University Hospital, Lille

Spots Global Cancer Trial Database for choline

Every month we try and update this database with for choline cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for choline

Every month we try and update this database with for choline cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for choline cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.