alanine and Cancer of Skin studies

Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.
alanine : An alpha-amino acid that consists of propionic acid bearing an amino substituent at position 2.

Research Excerpts

Excerpt	Relevance	Reference
"The authors conducted a phase II study of L-alanosine in 39 patients (19 without prior chemotherapy) in advanced malignant melanoma."	7.67	Phase II evaluation of L-alanosine (NSC-153353) for patients with disseminated malignant melanoma. ( Ahmann, DL; Creagan, ET; Green, SJ; Long, HJ, 1984)
" Ulipristal for uterine fibroids : market withdrawal due to risk of severe liver injury."	5.12	[Pharmacovigilance update]. ( Ekobena, P; Ivanyuk, A; Livio, F, 2021)
"The authors conducted a phase II study of L-alanosine in 39 patients (19 without prior chemotherapy) in advanced malignant melanoma."	3.67	Phase II evaluation of L-alanosine (NSC-153353) for patients with disseminated malignant melanoma. ( Ahmann, DL; Creagan, ET; Green, SJ; Long, HJ, 1984)
"Alzheimer's disease is characterized by the presence of cortical amyloid-beta (Aβ) protein plaques, which result from the sequential action of β-secretase and γ-secretase on amyloid precursor protein."	2.78	A phase 3 trial of semagacestat for treatment of Alzheimer's disease. ( Aisen, PS; Doody, RS; Farlow, M; He, F; Iwatsubo, T; Joffe, S; Kieburtz, K; Mohs, R; Raman, R; Sethuraman, G; Siemers, E; Sun, X; Thomas, RG; Vellas, B, 2013)
"Two human skin cell lines: Hs 895."	1.56	Roles of N-methyl-D-aspartate receptors and D-amino acids in cancer cell viability. ( Alatrash, N; Armstrong, DW; Berthod, A; Du, S; MacDonnell, FM; Sung, YS; Wang, Y; Wey, M, 2020)
"Obesity is associated with increased incidence and worse prognosis of more than one dozen tumor types; however, the molecular mechanisms for this association remain under debate."	1.51	Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation. ( Perry, RJ; Rabin-Court, A; Rodrigues, MR; Zhang, XM, 2019)

Research

Studies (12)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score at 16 Weeks After Cessation of Study Drug

Timeframe	Studies, this research(%)	All Research%
pre-1990	1 (8.33)	18.7374
1990's	3 (25.00)	18.2507
2000's	2 (16.67)	29.6817
2010's	4 (33.33)	24.3611
2020's	2 (16.67)	2.80

Authors	Studies
Du, S	1
Sung, YS	1
Wey, M	1
Wang, Y	1
Alatrash, N	1
Berthod, A	1
MacDonnell, FM	1
Armstrong, DW	1
Ekobena, P	1
Ivanyuk, A	1
Livio, F	1
Rabin-Court, A	1
Rodrigues, MR	1
Zhang, XM	1
Perry, RJ	1
Doody, RS	1
Raman, R	1
Farlow, M	1
Iwatsubo, T	1
Vellas, B	1
Joffe, S	1
Kieburtz, K	1
He, F	1
Sun, X	1
Thomas, RG	1
Aisen, PS	1
Siemers, E	1
Sethuraman, G	1
Mohs, R	1
Extance, A	1
Cummings, J	1
Liu, W	1
Kelly, JW	1
Trivett, M	1
Murray, WK	1
Dowling, JP	1
Wolfe, R	1
Mason, G	1
Magee, J	1
Angel, C	1
Dobrovic, A	1
McArthur, GA	1
Lamperska, KM	1
Przybyła, A	1
Kycler, W	1
Mackiewicz, A	1
Creagan, ET	1
Long, HJ	1
Ahmann, DL	1
Green, SJ	1
Herbst, RA	1
Gutzmer, R	1
Matiaske, F	1
Mommert, S	1
Kapp, A	1
Weiss, J	1
Arden, KC	1
Cavenee, WK	1
Izawa, M	1
Takayama, S	1
Shindo-Okada, N	1
Doi, S	1
Kimura, M	1
Katsuki, M	1
Nishimura, S	1
Vo, TK	1
Fischer, SM	1
Slaga, TJ	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Effect of γ-Secretase Inhibition on the Progression of Alzheimer's Disease: LY450139 Versus Placebo[NCT00594568]	Phase 3	1,537 participants (Actual)	Interventional	2008-03-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

ADAS-Cog11 consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. (NCT00594568)
Timeframe: Baseline (randomization), 16 weeks following treatment cessation

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score at 76 Weeks

Intervention	units on a scale (Least Squares Mean)
Placebo	6.59
100 mg LY450139	7.57
140 mg LY450139	7.90

ADAS-Cog11 was used as a primary efficacy measure. It consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. (NCT00594568)
Timeframe: Baseline (randomization), 76 weeks

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) Score at 16 Weeks After Cessation of Study Drug

Intervention	units on a scale (Least Squares Mean)
Placebo	6.19
100 mg LY450139	7.29
140 mg LY450139	7.68

ADAS-Cog12 is ADAS-Cog11 augmented with delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. (NCT00594568)
Timeframe: Baseline (randomization), 16 weeks following treatment cessation

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) Score at 76 Weeks

Intervention	units on a scale (Least Squares Mean)
Placebo	6.97
100 mg LY450139	8.27
140 mg LY450139	8.41

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) Score at 16 Weeks After Cessation of Study Drug

Intervention	units on a scale (Least Squares Mean)
Placebo	6.52
100 mg LY450139	7.98
140 mg LY450139	8.33

ADAS-Cog14 is ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, concomitant standard of care (SOC) medication. (NCT00594568)
Timeframe: Baseline (randomization), 16 weeks following treatment cessation

Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) Score at 76 Weeks

Intervention	units on a scale (Least Squares Mean)
Placebo	7.90
100 mg LY450139	9.30
140 mg LY450139	9.89

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory Score at 16 Weeks After Cessation of Study Drug

Intervention	units on a scale (Least Squares Mean)
Placebo	7.42
100 mg LY450139	8.97
140 mg LY450139	9.48

ADCS-ADL is a 23-item inventory developed as a Rater-administered questionnaire answered by the participant's caregiver. It measures performance of basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. (NCT00594568)
Timeframe: Baseline (randomization), 16 weeks following treatment cessation

Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory Score at 76 Weeks

Intervention	units on a scale (Least Squares Mean)
Placebo	-9.26
100 mg LY450139	-9.15
140 mg LY450139	-11.73

Change From Baseline in Amyloid Beta (Aβ) 1-42 Concentration in Spinal Fluid up to 76 Weeks

Intervention	units on a scale (Least Squares Mean)
Placebo	-8.76
100 mg LY450139	-10.13
140 mg LY450139	-12.70

Concentration of an amino peptide known as Aβ 1-42 in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. (NCT00594568)
Timeframe: Baseline (randomization), up to 76 weeks

Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) up to 76 Weeks

Intervention	picogram per milliliter (pg/mL) (Least Squares Mean)
Placebo	-86.16
100 mg LY450139	23.27
140 mg LY450139	-40.51

A radioactive tracer for PET that is a ligand for amyloid called AV-45. This permits the visualization of amyloid in the brains of Alzheimer's participants. The outcome reported is the composite summary of the standard uptake value ratio (SUVR) normalized to the cerebellar gray matter. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. (NCT00594568)
Timeframe: Baseline (randomization), up to 76 weeks

Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score at 76 Weeks

Intervention	ratio (Least Squares Mean)
Placebo	0.08
100 mg LY450139	0.06
140 mg LY450139	0.09

CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. (NCT00594568)
Timeframe: Baseline (randomization), 76 weeks

Change From Baseline in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Visual Analog Scale (VAS) Score at 76 Weeks

Intervention	units on a scale (Least Squares Mean)
Placebo	2.31
100 mg LY450139	2.73
140 mg LY450139	3.04

EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression; each has 3 severity levels (no, some, severe problems) coded to a 1-digit number (1-3). Digits are combined into 5-digit number describing health state. Numerals 1-3 are not added for total score. VAS assesses caregiver's impression of participant's overall health state; scores range from 0 to 100; Lower scores indicate greater disease severity. Least Squares (LS) Mean value controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. (NCT00594568)
Timeframe: Baseline (randomization), 76 weeks

Change From Baseline in Mini Mental State Examination (MMSE) Score at 76 Weeks

Intervention	units on a scale (Least Squares Mean)
Placebo	-1.41
100 mg LY450139	-7.49
140 mg LY450139	-5.33

MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, and ability to name objects, follow verbal and written commands, write a sentence, and copy figures) in elderly participants. The total score ranges from 0 to 30; Lower score indicates greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. (NCT00594568)
Timeframe: Baseline (randomization), 76 weeks

Change From Baseline in Neuropsychiatric Inventory (NPI) Score at 76 Weeks

Intervention	units on a scale (Least Squares Mean)
Placebo	-2.95
100 mg LY450139	-3.14
140 mg LY450139	-3.71

NPI assesses psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the participant's behavior. Total score ranges from 12 to 144; Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. (NCT00594568)
Timeframe: Baseline (randomization), 76 weeks

Change From Baseline in Phosphorylated-Tau (P-Tau) Concentration in Spinal Fluid

Intervention	units on a scale (Least Squares Mean)
Placebo	1.92
100 mg LY450139	3.31
140 mg LY450139	4.15

Concentration of p-tau in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. (NCT00594568)
Timeframe: Baseline (randomization), up to 76 weeks

Change From Baseline in Positron Emission Tomography (PET) Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) at 76 Weeks

Intervention	picogram per milliliter (pg/mL) (Least Squares Mean)
Placebo	9.75
100 mg LY450139	-6.26
140 mg LY450139	-5.13

Measurement of local cerebral glucose metabolism by PET using the radioactive tracer 18F-FDG. The outcome reported is the composite summary of the standard uptake value ratio (SUVR) normalized to the Pons. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. (NCT00594568)
Timeframe: Baseline (randomization), 76 weeks

Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) Score (Number of Hospitalizations) up to 76 Weeks

Intervention	ratio (Least Squares Mean)
Placebo	-0.08
100 mg LY450139	-0.12
140 mg LY450139	-0.11

Assesses healthcare resource utilization (formal and informal care). Information gathered on both caregivers (caregiving time, work status) and participants (accommodation and healthcare resource utilization) was collected from baseline and follow-up interviews; Reported number of hospitalizations per participant up to 76 weeks. Least Squares (LS) Mean value was controlled for age and investigator. (NCT00594568)
Timeframe: Baseline (randomization), up to 76 weeks

Change From Baseline in Tau Concentration in Spinal Fluid up to 76 Weeks

Intervention	hospitalizations/participant (Least Squares Mean)
Placebo	0.55
100 mg LY450139	0.66
140 mg LY450139	0.83

Concentration of total tau in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. (NCT00594568)
Timeframe: Baseline (randomization), up to 76 weeks

LY450139 Population Pharmacokinetics: Clearance of LY450139

Intervention	picogram per milliliter (pg/mL) (Least Squares Mean)
Placebo	75.11
100 mg LY450139	20.50
140 mg LY450139	61.00

Model estimated apparent oral clearance. Clearance is defined as the volume of plasma that is completely cleared of drug (LY450139) per unit time. (NCT00594568)
Timeframe: 6 weeks, 12 weeks, and 52 weeks

LY450139 Population Pharmacokinetics: Volume of Distribution of LY450139

Intervention	liter per hour (L/h) (Geometric Mean)
LY450139	18.8

Model-estimated apparent volume of distribution. Volume of distribution is a measure of the extent to which the drug distributes in the body. (NCT00594568)
Timeframe: 6 weeks, 12 weeks, and 52 weeks

Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at 52 Weeks

Intervention	liter (L) (Geometric Mean)
LY450139	66.8

Concentration of amino acid peptide, known as Aβ 1-42, in plasma. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. (NCT00594568)
Timeframe: Baseline (randomization), 52 weeks

Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks

Intervention	picogram per milliliter (pg/mL) (Least Squares Mean)
Placebo	3.86
100 mg LY450139	-5.97
140 mg LY450139	-19.95

The vMRI assessment of left and right hippocampal volume is reported. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. (NCT00594568)
Timeframe: Baseline (randomization), up to 76 weeks

Intervention	cubic millimeter (mm^3) (Least Squares Mean)
	Left Hippocampal Volume	Right Hippocampal Volume
100 mg LY450139	-75.34	-93.89
140 mg LY450139	-107.62	-112.40
Placebo	-96.54	-108.69

Article	Year
Roles of N-methyl-D-aspartate receptors and D-amino acids in cancer cell viability. Molecular biology reports, 2020, Volume: 47, Issue:9 Topics: Alanine; Amino Acids; Asparagine; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dizocilpine M	2020
Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation. PloS one, 2019, Volume: 14, Issue:6 Topics: Alanine; Breast Neoplasms; Cell Line, Tumor; Citrate (si)-Synthase; Colonic Neoplasms; Female; Gene	2019
Alzheimer's failure raises questions about disease-modifying strategies. Nature reviews. Drug discovery, 2010, Volume: 9, Issue:10 Topics: Alanine; Alzheimer Disease; Amyloid Precursor Protein Secretases; Azepines; Clinical Trials, Phase I	2010
What can be inferred from the interruption of the semagacestat trial for treatment of Alzheimer's disease? Biological psychiatry, 2010, Nov-15, Volume: 68, Issue:10 Topics: Alanine; Alzheimer Disease; Amyloid; Amyloid Precursor Protein Secretases; Azepines; Cognition Disor	2010
Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma. The Journal of investigative dermatology, 2007, Volume: 127, Issue:4 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alanine; Child; Female; Gene Frequency; Glutamic Acid; H	2007
The CDKN2a common variants: 148 Ala/Thr and 500 C/G in 3' UTR, and their association with clinical course of melanoma. Acta biochimica Polonica, 2007, Volume: 54, Issue:1 Topics: 3' Untranslated Regions; Adult; Aged; Alanine; Amino Acid Substitution; Cyclin-Dependent Kinase Inhi	2007
Phase II evaluation of L-alanosine (NSC-153353) for patients with disseminated malignant melanoma. American journal of clinical oncology, 1984, Volume: 7, Issue:5 Topics: Alanine; Antibiotics, Antineoplastic; Drug Evaluation; Female; Humans; Male; Melanoma; Middle Aged;	1984
Further evidence for ultraviolet light induction of CDKN2 (p16INK4) mutations in sporadic melanoma in vivo. The Journal of investigative dermatology, 1997, Volume: 108, Issue:6 Topics: Alanine; Alleles; Arginine; Carrier Proteins; Cyclin-Dependent Kinase Inhibitor p16; DNA, Neoplasm;	1997
Inhibition of chemical carcinogenesis in vivo by azatyrosine. Cancer research, 1992, Mar-15, Volume: 52, Issue:6 Topics: 9,10-Dimethyl-1,2-benzanthracene; Alanine; Animals; Antibiotics, Antineoplastic; Drug Screening Assa	1992
Effects of N-acyl dehydroalanines on phorbol ester-elicited tumor development and other events in mouse skin. Cancer letters, 1991, Volume: 60, Issue:1 Topics: Alanine; Animals; Cells, Cultured; Dinoprostone; Female; Free Radical Scavengers; Hyperplasia; Lumin	1991

alanine and Cancer of Skin