Chemotherapy-related late adverse effects on ovarian function in female survivors of childhood and young adult cancer: A systematic review

Overbeek, A.; Berg, Marleen H van den; Leeuwen, Flora E. van; Kaspers, Gertjan J. L.; Lambalk, Cornelis B.; Broeder, Eline van Dulmen‐den

doi:10.1016/j.ctrv.2016.11.006

Cited by 115 publications

(73 citation statements)

References 66 publications

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“…Chemotherapy is known to be an effective strategy for colon cancer patients. On the other hand, due to the relative nonselectivity of current anticancer drugs (malignant vs non-malignant cells), severe chemotherapy-related adverse reactions often limit the therapeutic effectiveness of these agents[3]. Therefore, novel therapeutic agents for treatment of colorectal cancer are needed.…”

Section: Introductionmentioning

confidence: 99%

Indole phytoalexin derivatives induce mitochondrial-mediated apoptosis in human colorectal carcinoma cells

Tischlerová

Kello

Budovská

et al. 2017

WJG

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AIMTo investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines.METHODSChanges in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and BrdU assay, allowing us to choose the most potent substance. Cell cycle alterations were analyzed using flow cytometric analysis. The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry, as well as acridine orange/propidium iodide (AO/PI) staining. The flow cytometry method also allowed us to measure changes in levels or activation states of other factors associated with apoptosis, such as poly (ADP-ribose) polymerase (PARP), caspase-3 and -9, cytochrome c, Bcl-2 family proteins, and also the integrity of the mitochondrial membrane. To evaluate activity of the transcription factors and proteins involved in signaling pathways we used Western blot analysis together with flow cytometry.RESULTSAmong the ten tested compounds, compound K-453 {(±)-trans-1,2-dimethoxy-2’-(3,5-bis-trifluoromethylphenylamino)spiro{indoline-3,5’[4’,5’]dihydrothiazol} exhibited the most potent activity with IC50 = 32.22 ± 1.14 μmol/L in human colorectal HCT116 cells and was thus selected for further studies. Flow cytometric analysis revealed a K-453-induced increase in the population of cells with sub-G1 DNA content, which is considered as a marker of apoptotic cell death. The apoptosis-inducing effect of compound K453 was also confirmed by annexin V/PI double staining and AO/PI staining. The apoptosis was associated with the loss of mitochondrial membrane potential, PARP cleavage, caspase-3 and caspase-9 activation, release of cytochrome c, as well as changes in the levels of Bcl-2 family members. Moreover, flow cytometry showed that compound K-453 stimulates phosphorylation of p38 MAPK but decreases phosphorylation of Akt and Erk 1/2. Activation of p38 MAPK was also confirmed using Western blot analysis. This analysis also revealed down-regulation of NF-κB1 (p50) and RelA (p65) proteins and the loss of their anti-apoptotic activity.CONCLUSIONIn our study compound K-453 exhibited an antiproliferative effect by induction of intrinsic apoptosis as well as modulation of several signaling pathways.

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Section: Introductionmentioning

confidence: 99%

Indole phytoalexin derivatives induce mitochondrial-mediated apoptosis in human colorectal carcinoma cells

Tischlerová

Kello

Budovská

et al. 2017

WJG

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“…Risk thresholds have decreased over time (e.g., decreasing from 10 to 7.5 to 4 grams/m 2 of cumulative cyclophosphamide dose for males), expanding the population that is considered to be "at-risk" (27). Radiation exposure to the testicles or ovaries can also impact their function (28,29). The degree that function is affected depends on type of radiotherapy, the precise location, the dose given, and even the age of the patient at the time of therapy (28,29).…”

Section: Oncologic Therapymentioning

confidence: 99%

“…Radiation exposure to the testicles or ovaries can also impact their function (28,29). The degree that function is affected depends on type of radiotherapy, the precise location, the dose given, and even the age of the patient at the time of therapy (28,29). Both alkylating agents and total body irradiation are commonly used in preparative regimens prior to hematopoietic stem cell transplantation (HSCT), resulting in gonadal insufficiency in up to 70-90% survivors (30,31).…”

Section: Oncologic Therapymentioning

confidence: 99%

Fertility counseling and preservation: considerations for the pediatric endocrinologist

Saraf

Nahata

2017

Transl. Pediatr

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Infertility is a distressing consequence of numerous pediatric medical conditions and treatments.The field of pediatric fertility preservation has expanded rapidly over the past decade, and clinical guidelines emphasize the importance of discussing infertility risk and fertility preservation options with patients and families in a timely manner. Understanding the various mechanisms and presentations of fertility issues across diagnoses is imperative to provide counseling to patients and families, and identify individuals who may benefit from fertility preservation. The goals of this manuscript are to outline current fertility preservation options in pediatrics, review populations at-risk for infertility that are seen in pediatric endocrinology, and discuss other important issues related to fertility preservation including ethical considerations.

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“…Treatment for these conditions, or consequences of the cancer itself, often leads to early menopause or menopausal symptoms. In a meta‐analysis of 45 studies of cancer survivors diagnosed from childhood to 40 years, the median age at menopause was found to be 44 years 6 . This may contribute to patient distress.…”

mentioning

confidence: 99%

Managing menopausal symptoms after cancer: an evidence‐based approach for primary care

Marino

McNamara

Hickey

2018

Medical Journal of Australia

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Summary Impaired ovarian function and menopausal symptoms are common after cancer treatment. Menopausal symptoms often occur at an earlier age in women with cancer, and may be more severe than in natural menopause; they may be the most persistent and troubling sequelae of cancer. A third of female patients with cancer report dissatisfaction with the quality and length of physician–patient discussions about reproductive health, including menopause. Systemic menopausal hormone therapy is the most effective treatment for menopausal symptoms, but it is not suitable for all patients after cancer — where it is unsuitable, alternative effective non‐hormonal treatments are available. Effective pharmacological agents available to treat vasomotor symptoms include selective serotonin reuptake inhibitors, serotonin–noradrenaline reuptake inhibitors, clonidine and gabapentin. There is increasing evidence supporting cognitive behavioural therapy for the treatment of vasomotor symptoms, in self‐help or group settings. Vaginal atrophy can be treated with vaginal (topical) oestrogen with minimal systemic absorption; topical vaginal lubricants may help with vaginal dryness and dyspareunia, with some evidence suggesting that silicone‐based products may be more effective than water‐based ones. Bone health may be impaired in post‐menopausal women with cancer or in cancer survivors, particularly in women with treatment‐related menopause or in women receiving anti‐oestrogen therapies; this should be managed in addition to menopausal symptoms. Primary care physicians should be aware of the troublesome and ongoing nature of menopausal symptoms after cancer, should discuss them with all patients after cancer treatment, and should consider treatment or referral to a specialist for appropriate management.

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Chemotherapy-related late adverse effects on ovarian function in female survivors of childhood and young adult cancer: A systematic review

Cited by 115 publications

References 66 publications

Indole phytoalexin derivatives induce mitochondrial-mediated apoptosis in human colorectal carcinoma cells

Indole phytoalexin derivatives induce mitochondrial-mediated apoptosis in human colorectal carcinoma cells

Fertility counseling and preservation: considerations for the pediatric endocrinologist

Managing menopausal symptoms after cancer: an evidence‐based approach for primary care

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