[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: Women with a higher birth weight are more likely to develop breast cancer later in life.

Document title: Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence.

Abstract sentences:
[0] BACKGROUND Emerging evidence suggests an association between female prenatal experience and her subsequent risk of developing breast cancer.
[1] Potential underlying mechanisms include variation in amounts of maternal endogenous sex hormones and growth hormones, germ-cell mutations, formation of cancer stem-cells, and other genetic or epigenetic events.
[2] We reviewed and summarised quantitatively the available data on intrauterine exposures and risk of breast cancer.
[3] METHODS We systematically searched for studies that assessed association between perinatal factors and risk of breast cancer.
[4] We reviewed separately each of the perinatal factors, including birthweight, birth length, parental age at delivery, gestational age, intrauterine exposure to diethylstilbestrol, twin membership, maternal pre-eclampsia or eclampsia, and other factors.
[5] FINDINGS We identified 57 studies published between Oct 1, 1980, and June 21, 2007.
[6] Increased risk of breast cancer was noted with increased birthweight (relative risk [RR] 1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]).
[7] Decreased risk of breast cancer was noted for maternal pre-eclampsia and eclampsia (0.48 [0.30-0.78]) and twin membership (0.93 [0.87-1.00]).
[8] No association was noted between risk of breast cancer and gestational age at birth (0.95 [0.71-1.26]) or maternal diethylstilbestrol treatment (1.40 [0.86-2.28]).
[9] INTERPRETATION The intrauterine environment contributes to the predisposition of women to breast cancer in adulthood.
[10] The in-utero mechanisms responsible for such predisposition need to be elucidated.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [6]
Explanation: Evidence states: "Increased risk of breast cancer was noted with increased birthweight (relative risk [RR] 1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]).". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: Women with a higher birth weight are more likely to develop breast cancer later in life.

Document title: Intrauterine environments and breast cancer risk: meta-analysis and systematic review

Abstract sentences:
[0] INTRODUCTION Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands.
[1] Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results.
[2] We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses.
[3] METHODS We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking.
[4] Meta-analyses using random effect models were employed to summarize the results.
[5] RESULTS We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk.
[6] Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for > or =3,000 g relative to <3,000 g).
[7] Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years.
[8] Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk.
[9] CONCLUSION Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [5]
Explanation: Evidence states: "RESULTS We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: aPKCz causes tumour enhancement by affecting glutamine metabolism.

Document title: Control of Nutrient Stress-Induced Metabolic Reprogramming by PKCζ in Tumorigenesis

Abstract sentences:
[0] Tumor cells have high-energetic and anabolic needs and are known to adapt their metabolism to be able to survive and keep proliferating under conditions of nutrient stress.
[1] We show that PKCζ deficiency promotes the plasticity necessary for cancer cells to reprogram their metabolism to utilize glutamine through the serine biosynthetic pathway in the absence of glucose.
[2] PKCζ represses the expression of two key enzymes of the pathway, PHGDH and PSAT1, and phosphorylates PHGDH at key residues to inhibit its enzymatic activity.
[3] Interestingly, the loss of PKCζ in mice results in enhanced intestinal tumorigenesis and increased levels of these two metabolic enzymes, whereas patients with low levels of PKCζ have a poor prognosis.
[4] Furthermore, PKCζ and caspase-3 activities are correlated with PHGDH levels in human intestinal tumors.
[5] Taken together, this demonstrates that PKCζ is a critical metabolic tumor suppressor in mouse and human cancer.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [3]
Explanation: Evidence states: "Interestingly, the loss of PKCζ in mice results in enhanced intestinal tumorigenesis and increased levels of these two metabolic enzymes, whereas patients with low levels of PKCζ have a poor prognosis.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: aPKCz causes tumour enhancement by affecting glutamine metabolism.

Document title: Control of Nutrient Stress-Induced Metabolic Reprogramming by PKCζ in Tumorigenesis

Abstract sentences:
[0] Tumor cells have high-energetic and anabolic needs and are known to adapt their metabolism to be able to survive and keep proliferating under conditions of nutrient stress.
[1] We show that PKCζ deficiency promotes the plasticity necessary for cancer cells to reprogram their metabolism to utilize glutamine through the serine biosynthetic pathway in the absence of glucose.
[2] PKCζ represses the expression of two key enzymes of the pathway, PHGDH and PSAT1, and phosphorylates PHGDH at key residues to inhibit its enzymatic activity.
[3] Interestingly, the loss of PKCζ in mice results in enhanced intestinal tumorigenesis and increased levels of these two metabolic enzymes, whereas patients with low levels of PKCζ have a poor prognosis.
[4] Furthermore, PKCζ and caspase-3 activities are correlated with PHGDH levels in human intestinal tumors.
[5] Taken together, this demonstrates that PKCζ is a critical metabolic tumor suppressor in mouse and human cancer.

[Assistant]
Label: CONTRADICTS
Rationale sentence ids: [5]
Explanation: Evidence states: "Taken together, this demonstrates that PKCζ is a critical metabolic tumor suppressor in mouse and human cancer.". This contradicts the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: cSMAC formation enhances weak ligand signalling.

Document title: The stimulatory potency of T cell antigens is influenced by the formation of the immunological synapse.

Abstract sentences:
[0] T cell activation is predicated on the interaction between the T cell receptor and peptide-major histocompatibility (pMHC) ligands.
[1] The factors that determine the stimulatory potency of a pMHC molecule remain unclear.
[2] We describe results showing that a peptide exhibiting many hallmarks of a weak agonist stimulates T cells to proliferate more than the wild-type agonist ligand.
[3] An in silico approach suggested that the inability to form the central supramolecular activation cluster (cSMAC) could underlie the increased proliferation.
[4] This conclusion was supported by experiments that showed that enhancing cSMAC formation reduced stimulatory capacity of the weak peptide.
[5] Our studies highlight the fact that a complex interplay of factors determines the quality of a T cell antigen.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [4]
Explanation: Evidence states: "This conclusion was supported by experiments that showed that enhancing cSMAC formation reduced stimulatory capacity of the weak peptide.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: mTORC2 regulates intracellular cysteine levels through xCT inhibition.

Document title: mTORC2 Regulates Amino Acid Metabolism in Cancer by Phosphorylation of the Cystine-Glutamate Antiporter xCT.

Abstract sentences:
[0] Mutations in cancer reprogram amino acid metabolism to drive tumor growth, but the molecular mechanisms are not well understood.
[1] Using an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism in cancer via phosphorylation of the cystine-glutamate antiporter xCT.
[2] mTORC2 phosphorylates serine 26 at the cytosolic N terminus of xCT, inhibiting its activity.
[3] Genetic inhibition of mTORC2, or pharmacologic inhibition of the mammalian target of rapamycin (mTOR) kinase, promotes glutamate secretion, cystine uptake, and incorporation into glutathione, linking growth factor receptor signaling with amino acid uptake and utilization.
[4] These results identify an unanticipated mechanism regulating amino acid metabolism in cancer, enabling tumor cells to adapt to changing environmental conditions.

[Assistant]
Label: SUPPORTS
Rationale sentence ids: [2, 3]
Explanation: Evidence states: "mTORC2 phosphorylates serine 26 at the cytosolic N terminus of xCT, inhibiting its activity. Genetic inhibition of mTORC2, or pharmacologic inhibition of the mammalian target of rapamycin (mTOR) kinase, promotes glutamate secretion, cystine uptake, and incorporation into glutathione, linking growth factor receptor signaling with amino acid uptake and utilization.". This supports the claim.


[User]
Determine whether the claim is SUPPORTS, CONTRADICTS, or NOT ENOUGH INFORMATION based only on the provided abstract. Use sentence indices as rationale evidence.

Claim: p16INK4A accumulation is  linked to an abnormal wound response caused by the microinvasive step of advanced Oral Potentially Malignant Lesions (OPMLs).

Document title: Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model

Abstract sentences:
[0] Monitoring cancer and aging in vivo remains experimentally challenging.
[1] Here, we describe a luciferase knockin mouse (p16(LUC)), which faithfully reports expression of p16(INK4a), a tumor suppressor and aging biomarker.
[2] Lifelong assessment of luminescence in p16(+/LUC) mice revealed an exponential increase with aging, which was highly variable in a cohort of contemporaneously housed, syngeneic mice.
[3] Expression of p16(INK4a) with aging did not predict cancer development, suggesting that the accumulation of senescent cells is not a principal determinant of cancer-related death.
[4] In 14 of 14 tested tumor models, expression of p16(LUC) was focally activated by early neoplastic events, enabling visualization of tumors with sensitivity exceeding other imaging modalities.
[5] Activation of p16(INK4a) was noted in the emerging neoplasm and surrounding stromal cells.
[6] This work suggests that p16(INK4a) activation is a characteristic of all emerging cancers, making the p16(LUC) allele a sensitive, unbiased reporter of neoplastic transformation.

[Assistant]
Label: NOT ENOUGH INFORMATION
Rationale sentence ids: []
Explanation: The provided abstract does not contain direct evidence to support or contradict the claim.