Cellular metabolic reprogramming is now recognized as a hallmark of tumors. Altered tumor metabolism determines the malignant biological behaviors and phenotypes of cancer. More recently, studies have begun to reveal that cancer cells generally exhibit increased glycolysis or oxidative phosphorylation (OXPHOS) for Adenosine Triphosphate(ATP)generation, which is frequently associated with drug resistance. The metabolism of drug-resistant cells is regulated by the PI3K/AKT/mTOR pathway which ultimately confer cancer cells drug resistance phenotype. The key enzymes involved in glycolysis and the key molecules in relevant pathways have been used as targets to reverse drug resistance. In this review, we highlight our current understanding of the role of metabolic symbiosis in therapeutic resistance and discuss the ongoing effort to develop metabolic inhibitors as anti-cancer drugs to overcome drug resistance to classical chemotherapy.
SETD7 is a methyltransferase that specifically catalyzes the monomethylation of lysine 4 on histone H3. A variety of studies has revealed the role of SETD7 in posttranslational modifications of non-histone proteins. However, the prognostic value of SETD7 on breast cancer and the ability of SETD7 of regulating intrinsic redox homeostasis has never been investigated. In this study, using The Cancer Genome Atlas (TCGA) database, we revealed that SETD7 was a potential prognostic marker of breast cancer. Median survival time of patients with low SETD7 expression (18.1 years) was twice than that of SETD7 low-expressed patients (9.5 years). We demonstrated that SETD7 promoted tumor cell proliferation and prevented cell apoptosis and that SETD7 delicately maintained the redox homeostasis through regulating the levels of GSH/GSSG and ROS. Further studies indicated that SETD7 was a positive activator of KEAP1-NRF2 pathway. Using dual luciferase assay, we revealed the role of SETD7 as a transcriptional activator of antioxidant enzymes. Downregulation of SETD7 in MCF7 and MDA-MB-231 cells impaired the expression of antioxidant enzymes and induces imbalance of redox status. Together, we proposed SETD7 as a prognostic marker of breast cancer and a novel antioxidant promoter under oxidative stress in breast cancer.
Purpose The predictive value of anti-Müllerian hormone (AMH) for ovarian dysfunction postchemotherapy is controversial. This study aimed to evaluate the value of serum AMH levels clinically and theoretically. Patients, Animals, and Methods We detected the serum estradiol, follicular stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels in 144 premenopausal women with breast cancer receiving cyclophosphamide-based chemotherapy. The hormone levels before and postchemotherapy were compared; the correlations among the hormones and amenorrhea and menstrual recovery were analyzed. In addition, the serum AMH levels were detected randomly in 177 normal healthy women and 36 normal female C57BL/6J mice of different ages; meanwhile, the status of ovarian follicles was also examined. Furthermore, 72 Balb/c nude mice with breast cancer were randomly assigned to three groups that received different doses of cyclophosphamide (CTX) (control, 100 mg/kg, and 200 mg/kg), and the alterations in serum AMH levels and ovarian follicles were recorded and analyzed. Results Chemotherapy-induced amenorrhea was associated with prechemotherapy AMH levels, E2 levels, and FSH levels ( P < 0.0001). The recovery of menstruation was associated with prechemotherapy AMH levels ( P < 0.0001), but not with E2 and FSH levels ( P > 0.05). In patients with breast cancer treated with chemotherapy, the serum AMH levels did not differ significantly between the pre- and post-chemotherapy periods in patients aged <35 years ( P > 0.05), whereas a dramatic reduction was detected in patients aged >35 years ( P < 0.0001). In healthy women, the serum AMH levels declined sharply after 35 years of age ( P < 0.0001) and remained relatively stable at a younger age. Similar results were obtained in experiments using normal mice. The cancer-bearing mice exposed to 200 mg/kg CTX exhibited a significant decline in AMH levels and a remarkable decrease in the number of primordial and growing follicles ( P < 0.0001). Conclusion Our results indicate that AMH is an efficient marker for predicting postchemotherapy ovarian function exclusively in premenopausal female patients with breast cancer aged >35 years.
Chemotherapy-induced ovarian dysfunction is a serious adverse effect in premenopausal patients with cancer. Gonadotrophin-releasing hormone analogs (GnRHa) protect ovarian function, but its molecular mechanisms have not yet been determined. In this study, we attempted to determine the previously unknown molecular mechanism by which such protection occurs. Serum anti-Müllerian hormone (AMH) levels were tested in tumor-bearing nude mice, a series of exploratory experiments were conducted. We discovered that GnRHa protects granulosa cells from chemotherapeutic toxicity in vivo and in vitro. We also showed that CTX-induced endoplasmic reticulum stress inhibits the secretion of AMH, and treatment with GnRHa relieves ER stress and the subsequent unfolded-protein response by modulating mTOR signaling to induce autophagy. The results of mechanistic studies indicated that GnRHa-modulated mTOR signaling to induce autophagy, which alleviated CTX-induced ER stress and promoted the secretion of AMH.
Background The predicting value of AMH for ovarian dysfunction after chemotherapy is controversial. This study is designed to evaluate the value of serum AMH clinically and theoretically. Patients, animals and methods We detected the serum estradiol, FSH and AMH in 144 pre-menopausal women with breast cancer receiving cyclophosphamide-based chemotherapy. The differences of hormones before and after chemotherapy were compared; the correlations among the hormones and amenorrhea, menstrual recovery were analyzed. In addition, serum AMH was detected randomly in 177 normal healthy women and 36 normal female C57BL/6J mice of different ages, meanwhile the status of ovary follicles was observed. Furthermore, 72 Balb/c nude mice with breast cancer were randomly assigned to three groups with different dosage of CTX (control, 100mg/kg, 200mg/kg), the alterations of serum AMH and ovary follicles were recorded and analyzed. Results Chemotherapy induced amenorrhea was associated with pre-chemo AMH level, E2 level and FSH level (P <0.0001). Recovery of menstruation was associated with pre-chemo AMH level (P <0.0001) but not E2 and FSH level (P >0.05). In breast cancer patients received chemotherapy, the serum AMH did not differ significantly between pre- and post- chemotherapy in patients younger than 35 years old (P>0.05), while dramatic decline was detected in patients over 35 years old (P<0.0001). In healthy women, the AMH level sharply declined after 35 years old ( P <0.0001) and remained relatively stable in early age. Similar results were obtained in normal mice experiments. The cancer-bearing mice exposed to 200mg/kg CTX endured significant decline of AMH levels and remarkable decrease of primordial and growing follicles (P <0.0001) Conclusion Our results indicate that AMH is effective for predicting post-chemo ovarian function only in premenopausal female breast cancer patients over 35 years old.
Background The predicting value of AMH for ovarian dysfunction after chemotherapy is controversial. This study is designed to evaluate the value of serum AMH clinically and theoretically. Methods We detected the serum estradiol, FSH and AMH in 144 pre-menopausal women with breast cancer receiving cyclophosphamide-based chemotherapy. The differences of hormones before and after chemotherapy were compared; the correlations among the hormones and amenorrhea, menstrual recovery were analyzed. In addition, serum AMH was detected randomly in 177 normal healthy women and 36 normal female C57BL/6J mice of different ages, meanwhile the status of ovary follicles was observed. Furthermore, 72 Balb/c nude mice with breast cancer were randomly assigned to three groups with different dosage of CTX (control, 100mg/kg, 200mg/kg), the alterations of serum AMH and ovary follicles were recorded and analyzed. Results Chemotherapy induced amenorrhea was associated with pre-chemo AMH level, E2 level and FSH level (P <0.0001). Recovery of menstruation was associated with pre-chemo AMH level (P <0.0001) but not E2 and FSH level (P >0.05). In breast cancer patients received chemotherapy, the serum AMH did not differ significantly between pre- and post- chemotherapy in patients younger than 35 years old (P>0.05), while dramatic decline was detected in patients over 35 years old (P<0.0001). In healthy women, the AMH level sharply declined after 35 years old ( P <0.0001) and remained relatively stable in early age. Similar results were obtained in normal mice experiments. The cancer-bearing mice exposed to 200mg/kg CTX endured significant decline of AMH levels and remarkable decrease of primordial and growing follicles (P <0.0001). Conclusion Our results indicate that AMH is effective for predicting post-chemo ovarian function only in premenopausal female breast cancer patients over 35 years old.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.