8 mei 2023: Bron: Biomedicine & Pharmacotherapy Volume 81, July 2016, Pages 160-165

Wanneer patiënten met AML = Acute Myeloide Leukemie naast hun chemokuren Haishengsu = is een gezuiverd eiwit gehaald uit de zeeschelp Tegillarca granosa, gebruiken dan geeft dat meer complete remissies en verbetert de kwaliteit van leven ook statistisch significant in vergelijking met patiënten uit de placebogroep.  

Dat blijkt uit de resultaten van een placebo gecontroleerde gerandomiseerde studie bij totaal 242 patiënten met AML = Acute Myeloide Leukemie die in aanmerking kwamen voor een analyse142 patiënten ontvingen Haishengsu en 109 patiënten ontvingen een placebo.

In het abstract worden geen exacte getallen genoemd maar wel schrijven de onderzoekers:
  • De percentages volledige remissie in de Haishengsu-behandelingsgroep waren allemaal hoger dan in de placebogroep met niet-recidiverende leukemie en recidiverende leukemie (p < 0,05).
  • Minder patiënten in de Haishengsu-groep ervoeren gastro-intestinale bijwerkingen van chemotherapie, terwijl meer patiënten een verhoogde voedselinname hadden en een toename in de Karnofsky Performance Status (KPS)-score (p <0,01).
  • In vitro was de expressie van P-gp en sorcin in de met Haishengsu behandelde cellen lager dan in de controlegroepcellen (p < 0,01).
Het studierapport is gedeeltelijk gratis in te zien maar voor het volledige studierapport met exacte cijfers moet worden betaald. 

Marine drug Haishengsu increases chemosensitivity to conventional chemotherapy and improves quality of life in patients with acute leukemia

https://doi.org/10.1016/j.biopha.2016.04.005Get rights and content

Abstract

Background

Pharmacological management of acute leukemia remains a challenge. A seashell protein Haishengsu (HSS) has been found to exert anticancer activities in recent in vitro studies. The aim of this study was to determine whether the addition of HSS to the conventional chemotherapies would increase chemosensitivity and improves quality of life in patients with acute leukemia.

Methods

Two hundred and forty-eight patients with acute leukemia were enrolled in a double-blind, and placebo-controlled study. In addition to conventional chemotherapy, 142 patients received HSS and 106 received placebo. In an in vitro study, the expression of P-gp was evaluated by flow cytometry in a drug-resistant leukemia cell line (K562/ADM cells). Sorcin was examined by Western blot.

Results

The complete remission rates in the HSS treatment group were all higher than in the placebo group with non-relapsing leukemia and relapsed leukemia (p < 0.05). Less patients in the HSS group experienced gastrointestinal side effects from chemotherapy, whereas more patients had increased food take and an increase in Karnofsky performance status (KPS) score (p <0.01). In vitro, the expression of P-gp and sorcin in the HSS treated cells were lower than in the control group cells (p < 0.01).

Conclusion

When added to conventional chemotherapy, HSS improves the complete remission rates and quality of life in patients with acute leukemia. The in vitro findings indicate that suppression of P-gp and sorcin genes in leukemia cells may be involved in the beneficial effects of HSS.

Introduction

Maintaining chemosensitivity to conventional chemotherapy and quality of life in patients with acute leukemia remain a challenge. The natural products may have an adjuvant effect when added to conventional chemotherapy in patients with cancers [1], [2]. Haishengsu (HSS) is a purified protein from Tegillarca granosa L. (Order Arcoida) which is a sea creature that contains a high concentration of proteins and vitamin B12 [3], [4], [5], [6], [7], [8], [9], , . When used as an adjuvant therapy, HSS was reported to improve clinical outcomes of patients undergoing conventional chemotherapy for lung or renal cancer [2], [8]. HSS has suppressive effects on leukemia K562 cells and transplanted tumor cells in animals [6], . HSS suppresses leukemia K562 cell growth by inhibiting the G0/G1 and S phases of the cell cycle [6], . It also induces apoptosis in leukemia cells by reducing expression of the apoptosis suppressor gene bcl-2, and increasing the expression of the apoptosis promoting gene box [6], . However, the effect of HSS on the clinical outcomes and quality of life of patients with acute leukemia is unknown.

Multi-drug resistance in cancer cells is a major hurdle to chemotherapy, and P-glycoprotein (P-gp) mediated efflux of xenobiotics is one of the major mechanisms involved in multi-drug resistance . Sorcin is a Ca2+-binding protein that regulates intracellular calcium homeostasis and plays a role in the induction of multi-drug resistance phenotypes in human cancer cell lines. In leukemia cells, sorcin was found to induce multidrug resistance through overexpression of P-gp . A recent study showed that down-regulation of sorcin induces cell apoptosis and chemosensitivity in a multidrug resistance cell line K562/A02 . The purpose of this study was to investigate the effect of HSS on chemosensitivity in patients with acute leukemia. To investigate the molecular mechanism of HSS on chemosensitivity, the in vitro effects of HSS on expression of the multi-drug resistance gene protein P-gp and sorcin was also studied in a drug-resistant leukemia cell line K562/ADM.

Section snippets

Patient selection

The institutional review board of Liaocheng People’s Hospital approved this study and written informed consent was obtained from all patients. From April 2006 to May 2013, 320 patients were recruited to this study from Liaocheng People’s Hospital and Haisheng Oncology Hospital (Qingdao, Shandong Province, China). Inclusion criteria were acute leukemia patients aged from 6 to 65 years. Exclusion criteria were those with liver or kidney dysfunction or those who were unable to give informed

Results

Seventy-two patients were excluded from the study due to compliance issues with the study protocols. In the end, 142 patients of HSS group and 106 patients of placebo group completed the study.

Discussion

The clinical outcomes among patients with acute leukemia have improved significantly in recent years , , . However, some patients continue to experience recurrence and eventually become refractory to treatment. The resistance of tumor cells to anticancer agents continues to be a problem that hinders successful chemotherapy. How to increase chemosensitivity in relapsed leukemia has become an important research objective , .

HSS has an antitumor effect in vitro and in vivo,

Conclusions

When added to conventional chemotherapy, HSS was associated with a higher complete remission rate in patients with acute leukemia, and a better quality of life. In a multidrug resistant leukemia cell line K562/ADM, HSS reduced the expression of multidrug-resistant gen protein P-gp and sorcin. These findings indicate that the addition of HSS to the conventional chemotherapy in patients with acute leukemia may improve chemosensitivity through suppressing multidrug resistance genes P-gp and sorcin.

Conflict of interest

Authors have no conflict of interest to declare.

Acknowledgements

The research was supported by a grant from National Natural Science Foundation of China (no. 8157377281403263), and from Shandong Province’s Science and Technology Development Projects (no: 2014GSF118141).

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