Methionine-restricted diet inhibits growth of MCF10AT1-derived mammary tumors by increasing cell cycle inhibitors in athymic nude mice.

BACKGROUND: Dietary methionine restriction (MR) improves healthspan in part by reducing adiposity and by increasing insulin sensitivity in rodent models. The purpose of this study was to determine whether MR inhibits tumor progression in breast cancer xenograft model and breast cancer cell lines. METHODS: Athymic nude mice were injected with MCF10AT1 cells in Matrigel® and fed a diet containing either 0.86 % methionine (control fed, CF), or 0.12 % methionine (MR) for 12 weeks. Plasma amino acid concentrations were measured by UPLC, and proliferation and apoptosis were examined using RT-PCR, immunohistochemistry, and Cell Titer 96® Aqueous One Solution Cell Proliferation assay. RESULTS: Mice on the MR diet had reduced body weight and decreased adiposity. They also had smaller tumors when compared to the mice bearing tumors on the CF diet. Plasma concentrations of the sulfur amino acids (methionine, cysteine, and taurine) were reduced, whereas ornithine, serine, and glutamate acid were increased in mice on the MR diet. MR mice exhibited decreased proliferation and increased apoptosis in cells that comprise the mammary glands and tumors of mice. Elevated expression of P21 occurred in both MCF10AT1-derived tumor tissue and endogenously in mammary gland tissue of MR mice. Breast cancer cell lines MCF10A and MDA-MB-231 grown in methionine-restricted cysteine-depleted media for 24 h also up-regulated P21 and P27 gene expression, and MDA-MB-231 cells had decreased proliferation. CONCLUSION: MR hinders cancer progression by increasing cell cycle inhibitors that halt cell cycle progression. The application of MR in a clinical setting may provide a delay in the progression of cancer, which would provide more time for conventional cancer therapies to be effective.

Dietary Methionine and Total Sulfur Amino Acid Restriction in Healthy Adults.

OBJECTIVES: Dietary restriction of methionine (Met) and cysteine (Cys) delays the aging process and aging-related diseases, improves glucose and fat metabolism and reduces oxidative stress in numerous laboratory animal models. Little is known regarding the effects of sulfur amino acid restriction in humans. Thus, our objectives were to determine the impact of feeding diets restricted in Met alone (MetR) or in both Met and Cys (total sulfur amino acids, SAAR) to healthy adults on relevant biomarkers of cardiometabolic disease risk. DESIGN: A controlled feeding study. SETTING AND PARTICIPANTS: We included 20 healthy adults (11 females/9 males) assigned to MetR or SAAR diet groups consisting of three 4-wk feeding periods: Control period; low level restriction period (70% MetR or 50% SAAR); and high level restriction period (90% MetR or 65% SAAR) separated by 3-4-wk washout periods. RESULTS: No adverse effects were associated with either diet and level of restriction and compliance was high in all subjects. SAAR was associated with significant reductions in body weight and plasma levels of total cholesterol, LDL, uric acid, leptin, and insulin, BUN, and IGF-1, and increases in body temperature and plasma FGF-21 after 4 weeks (P<0.05). Fewer changes occurred with MetR including significant reductions in BUN, uric acid and 8-isoprostane and an increase in FGF-21 after 4 weeks (P<0.05). In the 65% SAAR group, plasma Met and Cys levels were significantly reduced by 15% and 13% respectively (P<0.05). CONCLUSION: These results suggest that many of the short-term beneficial effects of SAAR observed in animal models are translatable to humans and support further clinical development of this intervention.

Acne scar revision update.

The typical patient with acne scarring has a variety of scar types. This article covers the choice and implementation of the several different techniques usually required to achieve optimal reconstruction.

Dermabrasion.

This article describes the method of dermabrasion and results obtained in various types of dermatologic conditions. Indications for surgery, appropriate patient selection, adjunctive surgical procedures, potential complications, and recent controversies are also addressed.

Liquid injectable silicone: techniques for soft tissue augmentation.

This article includes a description of the uses and indications of liquid injectable silicone and a discussion of the results obtained. Patient selection, indications, mechanism of action, potential complications, and adjunct procedures are also addressed.

Dermabrasion. As a complement to dermatology.

This article includes a description of the method of dermabrasion and a discussion of the results obtained in various types of dermatologic conditions. Indications for surgery, appropriate patient selection, adjunctive surgical procedures, potential complications, comparative modalities, and some recent controversies also are addressed.

Hair transplantation.

The history of hair transplantation and its recent developments are reviewed. The procedures, risks and benefits, avoidance of complications, and treatment of sequelae are discussed.

Subcutaneous incisionless (subcision) surgery for the correction of depressed scars and wrinkles.

BACKGROUND: A new method of subcuticular underming for the treatment of depressed cutaneous scars and wrinkles is introduced. OBJECTIVE: To define the newly coined term "Subcision" and to describe this minor surgical procedure for treating depressed scars and wrinkles. METHODS: A tri-beveled hypodermic needle is inserted through a puncture in the skin surface (hence, "incisionless" surgery), and its sharp edges are maneuvered under the defect to make subcuticular cuts or "-cisions." RESULTS: The depression is lifted by the releasing action of the procedure, as well as from connective tissue that forms in the course of normal wound healing. CONCLUSION: This technique is useful in treating a variety of cutaneous depressions, including scars and wrinkles.

Granulocytic sarcoma presenting as a solitary nodule of skin in a patient with Waldenstrom's macroglobulinemia. An immunohistochemical and electron-microscopic study.

While he was being treated for Waldenstrom's macroglobulinemia, a 75-year-old man developed an enlarging forearm skin nodule. On biopsy, the lesion appeared to be a malignant lymphoma. The tumor cells were negative for immunoglobulins but positive for lysozyme and alpha-1-antitrypsin. Therefore, the lesion was diagnosed as histiocytic lymphoma. Nine months later, an ipsilateral axillary lymph node biopsy revealed a small focus of tumor identical to that of the skin lesion. Three months after the lymph node biopsy, the patient developed acute myeloid leukemia. A reevaluation of the electron micrographs of the skin and lymph node lesion showed primary lysosomal granules within the tumor cell cytoplasm consistent with a diagnosis of leukemic infiltrates (granulocytic sarcoma); additionally, the naphthol AS-D chloracetate esterase activity of the skin lesion was positive, supporting the diagnosis of granulocytic sarcoma. This report shows that if not suspected, granulocytic sarcoma is difficult to diagnose in nonleukemia patients.