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30 december 2016: Bron: Journal of Pineal research

Het is algemeen bekend dat wie slecht slaapt of onrregelmatig werkt (ploegendienst) een groter risico loopt op ziek worden, waaronder daardoor ook een groter risico op kanker heeft. Dit risico wordt voornamelijk toegeschreven aan het tekort aan aanmaak van melatonine door het eigen lichaam. In gerelateerde artikelen kunt u lezen wat o.a. arts-bioloog drs. Engelbert hierover schrijft en waarom suppletie van melatonine naast de eigne aanmaak zinvol kan zijn. Zowel als preventie maar vooral ook als onderdeel van een behandeling van kanker.

Recent verscheen een studierapport dat ingaat op de rol die melatonine speelt bij de preventie en behandeling van vormen van spijsverteringskanker, waaronder naast vormen van darmkanker ook slokdarmkanker wordt bedoeld.

melatonine mechanisme(2)

Foto boven: Zo wordt melatonine aangemaakt door de pijnappelklier.

Het is een uitvoerig studierapport dat vooral ook ingaat op hoe melatonine het immuunsysteem beinvloed en hoe melatonine ook DNA schade kan repareren door invloed uit te oefenen op het apoptosisproces.

De onderzoekers baseerden van de onderstaande studies hun analyse in een review studie.

Tekst gaat verder onder grafiek.

Table 1. Melatonin disruption and gastrointestinal cancer
Research objectMeasuresOutcomeReference

  1. LL, constant light; OR, odds ratio; CI, confidence interval; NL, natural light; DMH, 1,2 dimethylhydrazine; and ACF, aberrant crypt foci.
Epidemiologic surveys
1658 colorectal patients with cancer and 3388 randomly selected population controls in Spain Face-to-face interviews and exposure assessment Having ever performed rotating shift work was associated with an increased risk for colorectal cancer (adjusted OR 1.33, 95% CI 1.15–1.55) compared with permanent day workers. ORs increased with cumulative years of rotating shift work and the OR for more than 30 yr of work 1.54 (1.22–1.94) Papantoniou et al. [44]
439 colon cancers, 236 rectal cancers, 228 male patients with stomach cancer and 512 controls in Montreal Face-to-face interviews Compared with men who never worked at night, the adjusted ORs among men who ever worked at night were 2.03 (95% CI: 1.43, 2.89) for colon cancer and 2.09 (95% CI: 1.40, 3.14) for rectal cancer. Equivocal evidence or no evidence was observed for cancers of the stomach (OR 1.34, 95% CI 0.85, 2.10) Parent et al. [36]
Experimental studies
Female CBA and transgenic HER-2/neu mice and rats Various light/dark regimens Exposure to constant illumination accelerated aging and enhanced tumorigenesis in female CBA and transgenic HER-2/neu mice. Exposure to NL and LL regimens induced tumorigenesis in rats, which could be prevented by melatonin Anisimov et al. [42]
Male rats LL environment (14 days; 300 lx), melatonin supplementation (10 mg/kg/day) and DMH treatment (125 mg/kg) LL induced ACF development and proliferative process. Melatonin supplementation controlled the development of dysplastic ACF diminishing preneoplastic patterns Kannen et al. [10]
Female rats Injection with DMH (21 mg/kg, 15 wk) and melatonin The serum melatonin level in rats with colon tumors was increased compared with controls. However, there was no diurnal rhythm of serum melatonin of colon tumor-bearing animals Anisimov et al. [122]
Melatonin level in patient with cancer
Patients with stomach cancer and colorectal cancer – A very low production of melatonin was found in male patients with stomach cancer. The production of melatonin was elevated in male patients with primary inoperable colorectal cancer Kvetnaia [123]
Patients with cancer of the stomach and large intestine – In patients with cancer, nocturnal excretion was lower than in daytime, while in healthy subjects, the situation was reversed Kvetnoĭ et al. [124]
Patient with colorectal carcinoma – During the night, melatonin concentration in patients with cancer was significantly lower than in controls Khoory et al. [125]
Patients with colorectal carcinoma – A significant decrease in amplitude of rhythm and secretion of melatonin at nocturnal hours was shown in the group of women with large intestine carcinoma. A significant decrease in mesor value and amplitude of melatonin rhythm was observed in the group of ill men Kos-Kudla et al. [126]

Grafiek boven: Collectively, melatonin disruption is closely correlated with gastrointestinal cancer, which hints at a possible therapeutic benefit of melatonin on these tumors.

En hieronder de studies waarin melatonine als aanvulling op andere behandelingen en medicijnen werd onderzocht:

Table 2. Studies on the drug synergy of melatonin in gastrointestinal cancer
Cancer categoriesNumber of patientsDrugs and doseOutcomeReferences

  1. OXA, Oxaliplatin; 5-FU, 5-fluorouracil; FA, folinic Acid; PELF, cisplatin + epirubicin + leucovorin + 5-FU; and IL-2, interleukin 2.
Experimental studies
Colon cancer SW480 and LoVo cells – Melatonin (1.0 mm) + Ursolic acid (10–60 μm) The combined treatment significantly enhanced the inhibition of cell viability and migration, promoted changes in cell morphology and spreading, and increased induction of apoptosis, thereby potentiating the effects of ursolic acid alone in colon cancer cells Wang et al. [11]
HT-29 human colon cancer cells – Melatonin (10−9–10−3 m) + Devazepide (10−9–10−5 m), or Lorglumide (10−6–10−3 m), or Proglumide (10−4–10−1 m) Melatonin and cholecystokinin-A antagonists were useful for controlling human colon cancer cell growth in culture and in combined therapy significantly increase their efficiency González-Puga et al. [127]
HT29 and healthy human lymphocytes – Melatonin (50 μm) + Irinotecan (7.5, 15, 30, and 60 μm) The combinational treatment resulted in an increase in the amount of DNA damage in HT29 cancer cells, but was not effective in inducing DNA damage in healthy human lymphocytes Kontek et al. [101]
LoVo and LoVo/ADR cells – Melatonin (0–100 pg/mL or 0–2000 pg/mL) + Doxorubicin (0.3 μm or 10 μm) Limited effects are observed on LoVo cell lines. A significant inhibition is caused by 100 pg/mL melatonin on the parental line and by 1000–2000 pg/mL melatonin on the multidrug resistant line; doxorubicin cytotoxicity is slightly and significantly increased at 2000 pg/mL Granzotto et al. [102]
Clinical trials
Metastatic colorectal cancer 30 Melatonin (20 mg/day) + Irinotecan (125 mg/m2/wk, 9 wk) The percent of disease control achieved in patients concomitantly treated with melatonin was significantly higher than that observed in those treated with chemotherapy alone (12 of 14 vs 7 of 16, p < 0.05) Cerea et al. [100]
Colorectal cancer and gastric cancer 223 Melatonin (20 mg/day) + OXA + 5-FU/FA, CPT-11, 5-FU/FA or PELF The overall tumor regression rate achieved in patients concomitantly treated with melatonin was significantly higher than that found in those treated with chemotherapy alone. Moreover, the 2-yr survival rate was significantly higher in the former group Lissoni, [32]
Colorectal cancer and gastric cancer 30 Melatonin (40 mg/day) + IL-2 (3 million IU/day) Tumor objective regression rate was significantly higher in patients treated with IL-2 and melatonin than in those receiving IL-2 alone. The survival at 1 yr was significantly higher in patients treated with IL-2 and melatonin than in the IL-2 group Lissoni et al. [128]
Gastrointestinal tract neoplasms 37 Melatonin (20 mg/day) + 5-FU plus FA The 1-yr survival rate and the objective tumor regression rate were significantly higher in patients concomitantly treated with melatonin than in those who received chemotherapy alone. Moreover, the toxicity was reduced in the concomitant administration of melatonin Lissoni et al. [103]

Het studierapport is nogal medisch technisch en voor mij te ingewikkeld om dit in goed Nederlands te vertalen. Maar een arts zal dit ongetwijfeld wel begrijpen. Anders lees de artikelen van Engelbert Valstar in gerelateerde artikelen er op na. En in bijna alle literatuurlijsten per vorm van kanker of naast chemo of bestraling staan wel 1 of meerdere studies met melatonine die in bijna alle gevallen een goed therapeutische effect geven.

Conclusie is ook van de ondezoekers van de reviewstudie dat suppletie van melatonine bij vormen van spijsverteringskanker in de vorm van een voedingssupplement bij een tekort zeker zinvol kan zijn. Al of niet naast andere medicijnen. Maar raadpleeg voor dosering enz. een goed gekwaificeerd orthomoleculair arts.

Hieronder een schema hoe melatonine werkzaam is binnen het immuunsysteem en apoptoseproces.

melatonine mechanisme 4

Het volledige studierapport: Melatonin as a treatment for gastrointestinal cancer: a review is gratis in te zien.

Het abstract hiervan staat hieronder met interessante referentielijst.

The impressive efficacy and safety of melatonin heralds it as a promising agent for gastrointestinal cancer treatment. It also deserves our attention given that several molecular mechanisms of action of melatonin have been established. The clarification of additional molecular processes of melatonin's oncostatic actions will help to facilitate better applications of melatonin to the problem of increased incidence of gastrointestinal cancer.

Review Article

Melatonin as a treatment for gastrointestinal cancer: a review

Abstract

Gastrointestinal cancer is a disease that affects the population worldwide with high morbidity and mortality. Melatonin, an endogenously produced molecule, may provide a defense against a variety of cancer types. In particular, the ability of melatonin to inhibit gastrointestinal cancer is substantial. In this review, we first clarify the relationship between the disruption of the melatonin rhythm and gastrointestinal cancer (based on epidemiologic surveys and animal and human studies) and summarize the preventive effect of melatonin on carcinogenesis. Thereafter, the mechanisms through which melatonin exerts its anti-gastrointestinal cancer actions are explained, including inhibition of proliferation, invasion, metastasis, and angiogenesis, and promotion of apoptosis and cancer immunity. Moreover, we discuss the drug synergy effects and the role of melatonin receptors involved in the growth-inhibitory effects on gastrointestinal cancer. Taken together, the information compiled here serves as a comprehensive reference for the anti-gastrointestinal cancer actions of melatonin that have been identified to date and will hopefully aid in the design of further experimental and clinical studies and increase the awareness of melatonin as a therapeutic agent in cancers of the gastrointestinal tract.

Concluding remarks

Melatonin, an endogenous indoleamine related to circadian rhythms, is a new agent that may be a candidate for use in the treatment of gastrointestinal cancer (Fig. 4). The application of melatonin for regulating carcinogenesis, development, and progression of gastrointestinal cancer has attracted attention as an appealing therapeutic strategy, partly due to its potent oncostatic effects and also because of its favorable safety profile. Numerous studies have documented the very low toxicity of melatonin over a wide range of doses [121]. The impressive efficacy and safety of melatonin heralds it as a promising agent for gastrointestinal cancer treatment. It also deserves our attention given that several molecular mechanisms of action of melatonin have been established. The clarification of additional molecular processes of melatonin's oncostatic actions will help to facilitate better applications of melatonin to the problem of increased incidence of gastrointestinal cancer.

Figure 4.

Figure 4.

A summary of mechanisms of the anti-gastrointestinal cancer actions of melatonin. Melatonin exerts its overall anti-gastrointestinal cancer effect through the following processes. Melatonin inhibits carcinogenesis, proliferation, angiogenesis, invasion, and metastasis of gastrointestinal cancer, while promoting apoptosis and cancer immunity. In addition, melatonin can be combined with other oncostatic agents to achieve a better therapeutic effect.

Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (81000938), the grants from the Excellent Doctoral Support Project of the Fourth Military Medical University (2013D01).

Conflict of interests

The authors declare no competing financial interest.

Ancillary

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darmkanker, melatonine, arts-bioloog drs. Engelbert Valstar, slapeloosheid, ploegendienst, slokdarmkanker, endeldarmkanker, rectumkanker


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