MASL for Oral Cancer

Recruiting at 3 trial locations

Overseen By Mahnaz Fatahzadeh

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rowan University

Must not be taking: Topical steroids

Disqualifiers: Cognitive impairments, Pregnant, Breastfeeding, others

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This project will evaluate the expression of a receptor called podoplanin (PDPN) in cells from oral cancers and precancerous lesions. We will also determine how sensitive oral cancer cells are to a potential drug called Maackia amurensis seed lectin (MASL).

Do I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used a topical steroid product within the last 2 weeks.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but it does mention that you should not have used a topical steroid product in the last 2 weeks.

What data supports the idea that MASL for Oral Cancer is an effective treatment?

The available research shows that MASL can effectively target a specific receptor called PDPN, which is involved in the growth and movement of oral cancer cells. Studies have demonstrated that MASL can stop the movement and growth of these cancer cells at very low concentrations. In experiments with zebrafish embryos, MASL significantly reduced the spread of oral cancer cells. Additionally, MASL was able to target cancer cells quickly and showed potential in reducing tumor growth in mice. Compared to another plant lectin, Abrus agglutinin, which also targets cancer progression, MASL specifically targets the PDPN receptor, making it a promising treatment for oral cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment MASL for oral cancer?

Research shows that MASL, a plant lectin, can target a specific receptor called PDPN on oral cancer cells, which helps to stop their growth and movement. This suggests that MASL might be effective in treating oral cancer by inhibiting cancer cell spread and survival. ^{1 2 3 4 5}

What safety data is available for MASL treatment in oral cancer?

The provided research does not contain specific safety data for MASL (Maackia amurensis seed lectin) in the context of oral cancer treatment. The studies focus on the potential mechanisms and effects of MASL on cancer cells, particularly its ability to target the PDPN receptor and inhibit cell growth and motility. However, there is no mention of safety assessments, toxicity studies, or clinical trial data for MASL in these articles. ^{1 3 6 7 8}

Is Maackia amurensis seed lectin (MASL) safe for humans?

The available research does not provide specific safety data for Maackia amurensis seed lectin (MASL) in humans, but it has been studied for its ability to target cancer cells. ^{1 3 6 7 8}

Is MASL a promising drug for oral cancer?

Yes, MASL is a promising drug for oral cancer because it can target specific receptors in cancer cells that are usually resistant to standard treatments. This makes it a novel option for treating oral cancer. ^{1 2 9 10 11}

How is the drug MASL different from other treatments for oral cancer?

MASL is unique because it targets the PDPN receptor, which is often more active in oral cancer cells compared to normal cells, making it a novel option for treating oral cancer that is resistant to standard chemotherapy. ^{1 2 9 10 11}

Eligibility Criteria

This trial is for adults with white or red spots/lesions in the mouth, diagnosed as oral cancer or precancer. It's open to smokers and non-smokers who are generally healthy, have good organ function, and no severe illnesses. Pregnant women, breastfeeding mothers, those unable to consent, on steroids recently or with hearing/language issues can't join.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I am scheduled for a biopsy or surgery as part of my treatment plan.

Both smokers and non-smokers can participate.

Exclusion Criteria

I have used a topical steroid in the last 2 weeks.

You have difficulty hearing or communicating verbally.

Abstinence or use of adequate contraception will be required for women of childbearing potential and men of reproductive potential.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Evaluation

Measure morphology and podoplanin (PDPN) expression by immunohistochemistry of cells included in initial biopsies of oral lesions

1 day to 4 weeks

Treatment

Patients receive lozenges containing MASL or placebo to evaluate the effect on PDPN expression and morphology of OSCC cells

4 weeks

Follow-up

Participants are monitored for changes in PDPN expression and morphology of OSCC cells post-treatment

4 weeks

Treatment Details

Interventions

• MASL

Trial Overview The study tests MASL's effectiveness against oral cancer by comparing it to a placebo. Participants will be randomly assigned to receive either MASL or an inactive substance without knowing which one they're getting.

Participant Groups

Group I: MASL treated Experimental Treatment 1 Intervention

Patients treated with lozenge containing MASL

Group II: Placebo treated Placebo Group 1 Intervention

Patients treated with lozenge without MASL

Who Is Running the Clinical Trial?

Rowan University

Lead Sponsor

Trials

25

Recruited

3,000+

Rutgers University

Collaborator

Trials

127

Recruited

2,814,000+

Findings from Research

Maackia amurensis seed lectin (MASL) has been shown to significantly inhibit the growth and movement of oral squamous cell carcinoma (OSCC) cells by affecting the expression of about 27% of genes related to key signaling pathways, including TGFβ-SMAD and JAK-STAT.

MASL not only decreased the expression of important cancer-related genes like PDPN and SMAD5 but also inhibited critical signaling activities, suggesting its potential as a novel treatment for oral cancer, especially when used in combination with standard chemotherapy agents like doxorubicin and 5-fluorouracil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Maackia amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways. Hamilton, KL., Sheehan, SA., Retzbach, EP., et al.[2022]

MAL-II, a lectin from Amur seeds, demonstrated significant antitumor activity against human anaplastic thyroid cancer cells (8505C) by altering the expression of various cancer-related and anticancer genes, as shown through RNA-Seq analysis.

The treatment with MAL-II led to the downregulation of several cancer-promoting genes and the upregulation of anticancer genes, indicating its potential as a therapeutic candidate by affecting key signaling pathways like Ras, p53, and apoptosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RNA-Seq transcriptome analysis reveals Maackia amurensis leukoagglutinin has antitumor activity in human anaplastic thyroid cancer cells. Bektas, S., Kaptan, E.[2022]

A lectin from Maackia amurensis (MASL) effectively targets the podoplanin (PDPN) receptor, which is involved in promoting tumor cell motility and metastasis, inhibiting cancer cell growth at very low concentrations (nanomolar levels).

This lectin remains biologically active after passing through the digestive system, allowing it to enter the bloodstream and inhibit melanoma cell growth and migration, suggesting its potential as a dietary agent in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration. Ochoa-Alvarez, JA., Krishnan, H., Shen, Y., et al.[2021]

A monoclonal antibody (NZ-1) and a lectin (MASL) targeting the PDPN receptor effectively inhibited the migration of oral squamous cell carcinoma (OSCC) cells at low concentrations and reduced cell viability at higher concentrations, indicating their potential as therapeutic agents.

Both NZ-1 and MASL induced cell death through a unique mechanism involving mitochondrial membrane permeability transition, leading to nonapoptotic necrosis, and MASL was particularly effective in reducing OSCC spread in zebrafish models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms. Ochoa-Alvarez, JA., Krishnan, H., Pastorino, JG., et al.[2022]

Abrus agglutinin (AGG) effectively inhibits epithelial-to-mesenchymal transition (EMT) in oral cancer cells by activating p73, which suppresses the expression of Snail, a key protein involved in cancer progression.

AGG not only reduces the invasiveness and stemness of oral cancer cells but also alters the expression of critical proteins, leading to decreased Snail and increased E-cadherin levels in treated tumor samples, indicating its potential as a therapeutic agent against oral cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

p73 induction by Abrus agglutinin facilitates Snail ubiquitination to inhibit epithelial to mesenchymal transition in oral cancer. Sinha, N., Meher, BR., Naik, PP., et al.[2020]

Machilin D (Mach), a compound isolated from Saururus chinensis, exhibits significant cytotoxic effects against oral squamous cell carcinoma (OSCC) cells, indicating its potential as a therapeutic agent for this aggressive cancer.

The mechanism of action for Mach involves promoting apoptosis and autophagy while inhibiting necroptosis, primarily through the suppression of key signaling pathways like FAK/Src and PI3K/AKT/mTOR, which are crucial for cancer cell survival and proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells. Yun, HM., Kwon, YJ., Kim, E., et al.[2023]

WSMoL, a water-soluble lectin from Moringa oleifera, demonstrated significant antitumor activity in mice with sarcoma 180 tumors, particularly at safe doses of 5 and 10 mg/kg, leading to reduced tumor weight and cell dissemination.

At a higher dose of 200 mg/kg, WSMoL showed acute toxicity with 60% mortality, but at 100 mg/kg, it was safe with no deaths and no significant changes in blood parameters, indicating a need for careful dosing in therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and antitumor activity of the water-soluble lectin from Moringa oleifera Lam. Seeds (WSMoL) in sarcoma 180-bearing mice. Brito, JS., Marinho, AO., Coelho, LCBB., et al.[2023]

In a study involving rats on total parenteral nutrition, both concanavalin-A and epidermal growth factor significantly increased cell proliferation in the small intestine and colon, indicating their potential as growth-promoting agents.

While concanavalin-A did not affect crypt branching, it worked synergistically with epidermal growth factor in the mid small intestine, suggesting that concanavalin-A could enhance intestinal function in vivo, contrary to its inhibitory effects observed in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the effects of concanavalin-A and epidermal growth factor on epithelial cell proliferation in the rat intestine. Fitzgerald, AJ., Jordinson, M., Rhodes, JM., et al.[2019]

Maackia amurensis agglutinin shows strong reactivity with non-small cell lung cancer (NSCLC) cells and tissue samples, indicating its potential as a diagnostic tool for NSCLC.

This lectin not only identifies NSCLC cells but also induces apoptosis in these cells through a specific mechanism involving the regulation of apoptosis-related proteins, suggesting its potential as a therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential importance of Maackia amurensis agglutinin in non-small cell lung cancer. Mehta, S., Chhetra, R., Srinivasan, R., et al.[2016]

The study identified the N-linked glycan structure of Maackia amurensis leukoagglutinin (MAL), revealing eight glycans that are crucial for its lectin activities, particularly in binding to sialoglycoproteins.

Removal of high-mannose-type glycans from MAL significantly reduced its ability to agglutinate cells and detect human breast cancer MCF-7 cells, indicating that these glycans are essential for its functional efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of selective cleavage of high-mannose-type glycans of Maackia amurensis leukoagglutinin on sialic acid-binding activity. Kim, BS., Hwang, HS., Park, H., et al.[2016]

The study identified and sequenced cDNA clones for leukoagglutinin (MAL) from Maackia amurensis, revealing it has a high similarity (86.2% identity) to Maackia amurensis hemagglutinin (MAH).

Key amino acid substitutions in MAL and MAH were found to be critical for binding to sialic acid residues, as mutations at specific positions resulted in loss of binding ability, highlighting the importance of these residues in the lectins' function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sialic acid-binding motif of Maackia amurensis lectins. Yamamoto, K., Konami, Y., Irimura, T.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Effects of Maackia amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

RNA-Seq transcriptome analysis reveals Maackia amurensis leukoagglutinin has antitumor activity in human anaplastic thyroid cancer cells. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Plant lectin can target receptors containing sialic acid, exemplified by podoplanin, to inhibit transformed cell growth and migration. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

p73 induction by Abrus agglutinin facilitates Snail ubiquitination to inhibit epithelial to mesenchymal transition in oral cancer. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Toxicity and antitumor activity of the water-soluble lectin from Moringa oleifera Lam. Seeds (WSMoL) in sarcoma 180-bearing mice. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Comparison of the effects of concanavalin-A and epidermal growth factor on epithelial cell proliferation in the rat intestine. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Potential importance of Maackia amurensis agglutinin in non-small cell lung cancer. [2016]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of selective cleavage of high-mannose-type glycans of Maackia amurensis leukoagglutinin on sialic acid-binding activity. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Sialic acid-binding motif of Maackia amurensis lectins. [2019]