Documentation of Patient Outcomes for the Combination Treatment of Sodium Stibogluconate and Allopurinol in Complicated Cutaneous Leishmaniasis in Ethiopia

Outcomes of patients receiving SSG and Allopurinol combination have never been documented systematically in Ethiopia. Therefore, it is not known how effective this combination is. This study will provide evidence to help clinicians make the best choice regarding treatment for complicated cutaneous leishmaniasis (CL) cases. Due to diversity in host-pathogen interactions across the different CL forms, early immunological correlates associated with treatment responsiveness and unresponsiveness could help treatment recommendation and provide us with the basis to develop new diagnostic and treatment strategies.
This study aims to document treatment outcomes of patients with cLCL, MCL, and DCL receiving systemic treatment using SSG and Allopurinol combination within a routine care setting located in a highly endemic area in Ethiopia.

Start Date15 Feb 2021

Sponsor / Collaborator

Instituut voor Tropische Geneeskunde

[+1]

NCT04906031 / Unknown statusPhase 2IIT

Sodium Stibogluconate in the Myelodysplastic Syndromes/Acute Myeloid Leukemia With One of the 65 Defined p53 Mutations That Can be Functionally Rescued by Sodium Stibogluconate

To evaluate the safety and effectiveness of Sodium Stibogluconate in the treatment of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) with p53 mutation from a defined list. The list includes 65 p53 mutations that were experimentally confirmed to be pharmacologically restored with tumor-suppressive function by antimonials.

Start Date01 Jun 2020

Sponsor / Collaborator

The First Affiliated Hospital of Jinan University

[+1]

SLCTR/2016/025 / RecruitingNot ApplicableIIT

Efficacy and safety of thermotherapy by Hand-held Exothermic Crystallization Thermotherapy device compared to ThermoMed device, for treatment of cutaneous leishmaniasis showing poor response to intralesional sodium stibogluconate in Sri Lanka - A randomized controlled pilot study

Start Date17 Oct 2016

Sponsor / Collaborator-

100 Clinical Results associated with Sodium stibogluconate

100 Translational Medicine associated with Sodium stibogluconate

100 Patents (Medical) associated with Sodium stibogluconate

1,667

Literatures (Medical) associated with Sodium stibogluconate

01 Oct 2024·Journal of Proteomics

Characterizing Leishmania infantum-induced resistance to trivalent stibogluconate (SbIII) through deep proteomics

Article

Author: Ramírez, Juan David ; Patiño, Luz H. ; López, Julio ; Patiño, Luz H ; Julio, López ; Antonio, Muro ; Manzano, Raúl ; Muro, Antonio ; Castillo-Castañeda, Adriana

Leishmania infantum belongs to the L. donovani complex, which includes species associated with visceral leishmaniasis. Traditionally, antimonial compounds have served as the primary antiparasitic treatment for all clinical forms of leishmaniasis. However, the global spread of resistance to these compounds has posed a significant challenge in the treatment in some regions. In this study, we aimed to investigate resistance to trivalent sodium stibogluconate in vitro using promastigotes from a wild strain of L. infantum. We compared the growth rates and proteomic profiles of wild-type and resistant line conducting label-free quantitative mass spectrometry-based proteomic analyses. Statistical and bioinformatics analyses were employed to evaluate the significance of protein concentration changes, protein identity annotation, GO term analysis, biosynthetic pathways, and protein-protein interactions. Our findings revealed that the resistant line displayed a notable reduction in growth rate. Proteomic data unveiled similar protein concentrations per cell in both groups but with differing molecule copy numbers. We identified 165 proteins with increased concentration, these were associated with transcription and translation activities, lipid metabolism, energy metabolism, and peroxisome biogenesis. In the decreased protein groups were 56 proteins linked to metal acquisition and metabolism, particularly iron. These results suggest a novel perspective on antimonial resistance, highlighting the importance of post-transcriptional and post-translational regulation, alongside energy expenditure compensation and alterations in organelle membrane lipid composition in antimonial-resistant parasites. Overall, our study provides insights into the proteomic profile of stibogluconate-resistant strain, contributing to our general understanding of the complex landscape of antiparasitic resistance in L. infantum. SIGNIFICANCE: Species within the Leishmania donovani complex are implicated in cases of visceral leishmaniasis in the world. Leishmania infantum is a species that predominates in regions spanning the Mediterranean Basin, the Middle East, Central Asia, South and Central America. Antimonials were the first treatment for leishmaniasis, however in the last decades, the resistance has emerged in subregions like India, where it is not a therapeutic option. In contrast, sodium stibogluconate (SbIII) remains the first-line treatment in the Americas. Unfortunately, the emergence of resistance has outpaced the development of new therapeutic options, thereby becoming a critical point in the struggle against the disease. In this study we performed an in-depth proteomic analysis with liquid chromatography mass-mass spectrometry (LC-MS/MS) on L. infantum with Sb-induced resistance in vitro. Results showed a complex proteomic adaptation in the resistant line, involving transcriptional and translational proteins, energy compensation, and homeostasis maintenance. These insights contribute to understanding the molecular adaptation in the parasite and provide information to new investigations related to therapeutics development.

01 Sep 2024·Phytomedicine

Lung-intestinal axis, Shuangshen granules attenuate lung metastasis by regulating the intestinal microbiota and related metabolites

Article

Author: Maolan, Ayidana ; Luo, Yue ; Ren, Xiaoling ; Hua, Baojin ; Sun, Tianheng ; Li, Yue ; Shi, Bolun ; Li, Juan ; He, Shulin ; Zhang, Xinyue ; Zhang, Guanghui ; Liu, Rui ; Hu, Jiaqi ; Qi, Xin

BACKGROUNDBased on the proposed lung-intestinal axis, there is a significant correlation between the microbiota and lung metastasis. Targeting the microbial composition is valuable in modulating the host response to cancer therapeutics. As a traditional Chinese medicine (TCM) formula, Shuangshen granules (SSG) are clinically useful in delaying lung metastasis, but its underlying mechanisms remain unknown.METHODSThe C57BL/6N mice were chosen to establish the Lewis lung cancer models. The broad-spectrum antibiotics (ABX) group was set up to estimate the effect of microbiota composition on metastasis. The therapeutic effects of different doses of SSG in treating lung metastasis were investigated through histopathology, immunohistochemistry, and Western blot analysis methods. Additionally, the phenotype of tumor-associated macrophages (TAMs) in the lung and blood was evaluated by flow cytometry. The fecal microbiota transplantation (FMT) and negative control (ABX plus high dose SSG group) experiments were also designed to assess intestinal microbiota's role in SSG intervention's outcome in lung metastasis. The 16S rRNA amplicon sequencing and Untargeted metabolomic analysis were used to analyze intestinal microbiota and metabolite changes mediated by SSG in tumor-bearing mice with lung metastasis.RESULTABX could observably lead to intestinal microbiota dysbiosis and enhance metastasis. SSG showed a significant chemopreventive effect in lung metastasis, reduced metastatic nodules and the expression levels of pre-metastatic niche biomarkers, and enriched the ratio of CD86+F4/80+CD11b+ cells, while FMT delayed metastasis similarly. The analysis of microbiota and metabolites revealed that SSG significantly enriched probiotics in feces, including Akkermansia muciniphila, Lachnoclostridium sp YL32, Limosilactobacillus reuteri, and potential anti-cancer serum metabolites, including Ginsenoside Rb1, Isoquinoline, Betulin and so on. We also investigated the mechanism of SSG protection against lung metastasis and showed that SSG regulated microbiota, improved TAMs polarization, and inhibited the expression of the NF-κB pathway.CONCLUSIONThe results presented in our article demonstrated that SSG improved TAMs polarization and inhibited the NF-κB pathway by alleviating intestinal microbiota imbalance and metabolic disorders in tumor-bearing mice, resulting in delayed lung metastasis.

01 Sep 2024·Heliyon

Shenqi Sanjie Granules induce Hmox1-mediated ferroptosis to inhibit colorectal cancer

Article

Author: Liu, Yu ; Yang, Shasha ; Gao, Jiguang ; Hu, Weihua ; Ma, Shengli ; Chen, Meng ; Dai, Haiming ; Cui, Qianwen ; Hu, Lei ; Xu, Xiaohui ; Yang, Jianke ; Ji, Wenbo

BackgroundBecause adverse reactions or drug resistance are often found after current chemotherapies for metastatic colorectal cancer (mCRC), new treatments are still in demand. Shenqi Sanjie Granules (SSG), an antitumor compound preparation of traditional Chinese medicine, has been recognized for its ability in clinical practice of oncotherapy. Nevertheless, the precise effects of SSG in colorectal cancer (CRC) and underlying mechanisms through which SSG inhibits CRC remain uncertain. The current study aimed to evaluate the anti-CRC activity of the Chinese herbal compound preparation SSG and investigate the underlying mechanisms of action.Materials and methodsInitially, nine distinct cancer cell lines, including five CRC cell lines, one breast cancer cell line, two lung adenocarcinoma cell lines and one cervical cancer cell line, were used to evaluate the antitumor activity of SSG, and the mouse CRC cell line CT26 were used for further research. In vitro experiments utilizing diverse assays were conducted to assess the inhibitory effects of the SSG on CT26. Furthermore, subcutaneous syngeneic mouse model and AOM (azoxymethane)/DSS (dextran sodium sulfate) induced in-situ colitis-related mouse CRC model were used to evaluate the antitumor potential and biotoxicity of SSG in vivo. To elucidate the underlying molecular mechanisms, transcriptome sequencing and network pharmacology analysis were performed. Meanwhile, verification is carried out with quantitative real-time PCR (qRT-PCR) and flow cytometry (FCM) analysis.ResultsOur in vitro inhibition study showed that SSG could effectively inhibit CRC cell line CT26 growth and metastasis, and induce cell death. Neither of apoptosis inhibitor, necroptosis inhibitor, ferroptosis inhibitor, but the combination of the three diminished SSG-induced cell death, suggesting that multiple cell death pathways were involved. Both the syngeneic CRC model and the in-situ CRC model indicated SSG inhibited CRC in vivo with few toxic side effects. Further mechanistic study suggested SSG treatment activated the ferroptosis pathway, particularly mediated by Hmox1, which was upregulated scores of times. Network pharmacology analysis indicated that the active ingredients of SSG, including Quercetin, Luteolin and Kaempferol were potential components directly upregulated Hmox1 expression.ConclusionsCollectively, our findings indicate that the administration of SSG has the potential to inhibit CRC both in vitro and in vivo. The mechanism by which this compound preparation exerts its action is, at least partly, the induction of ferroptosis through upregulating Hmox-1 by its three active ingredients Quercetin, Luteolin and Kaempferol.

100 Deals associated with Sodium stibogluconate

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KEGG	Wiki	ATC	Drug Bank
D00582	Sodium stibogluconate	P01CB02	DB05630

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Leishmaniasis	-	GSK Plc	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Leishmaniasis, Cutaneous	Phase 1	US	-	-
Solid tumor	Phase 1	US	-	-

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03129646 (Pubmed)	Phase 3	Leishmaniasis, Visceral	439	Paromomycin plus Miltefosine	kxcdyxvwzw(mczokvijxu) = innvzbctml plavemhpxe (qiemknxorh, -6.2 to 7.4)	Positive	27 Sep 2022
				Sodium Stibogluconate plus Paromomycin	kxcdyxvwzw(mczokvijxu) = cirezbeyeh plavemhpxe (qiemknxorh, -6.2 to 7.4)
NCT01067443 (Pubmed \| PLoS Negl Trop Dis)	Phase 2	Leishmaniasis, Visceral	151	AmBisome + SSG	(fsxomcgupw) = igovbzgoyc oiaysxqqaj (ksljlnwfcq, 73 - 92) View more	-	01 Sep 2016
				AmBisome + miltefosine	(fsxomcgupw) = fzdsmtarzg oiaysxqqaj (ksljlnwfcq, 73 - 92) View more
Pubmed \| J Dermatolog Treat	Not Applicable	-	154	Intralesional sodium stibogluconate	rrdjnsvlks(ycrijrthya) = rrfantkadi klqwqotwwg (qrmccmiphq ) View more	-	01 Sep 2010
				Intralesional 7% hypertonic sodium chloride	rrdjnsvlks(ycrijrthya) = rhfztvadzt klqwqotwwg (qrmccmiphq ) View more

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