The research of our team is mainly focused on the biology of cancer, in different aspects, and consistently, we pursue different perspectives as an integrated research plan. Cancer is a multifactorial disease with genetics and environment (including lifestyle) playing important roles in its appearance. Accordingly, cancer research should be as complicated as its biology, and following one approach for cancer research isn't as helpful as studying cancer biology from different aspects. Our team works in an integrated manner, meaning we pursue a goal from different directions using different strategies. Our perspectives for performing research in cancer biology are cancer genetics, cancer signaling, computational biology, and multidisciplinary studies. We pursue a defined goal in our studies using these mentioned styles. Currently, our team is focused on cancers of the gastrointestinal tract especially pancreatic cancer as the "most lethal common cancer". Some of our research highlights are mentioned in the following.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies and remains a major cause of cancer-related mortality worldwide. Despite advances in diagnostic techniques and therapeutic strategies, the prognosis of pancreatic cancer remains poor because the majority of patients are in metastatic stage at the time of diagnosis. Gemcitabine has long served as a cornerstone of systemic therapy for pancreatic cancer, either alone or in combination with other chemotherapeutic agents. However, considerable interindividual variation exists in treatment response and survival, highlighting the need for reliable biomarkers that can predict clinical outcome and guide personalized therapeutic decisions. Germline genetic variants represent attractive biomarker candidates because they can be assessed before treatment initiation and remain stable throughout the course of disease. SH3D21 has recently emerged as a gene of interest after a genome-wide CRISPR/Cas9 screening identified it as a modulator of gemcitabine sensitivity in pancreatic cancer cells. The clinical significance of genetic variation within SH3D21 had not previously been investigated.
We evaluated the association between the SH3D21 rs34416442 polymorphism and overall survival in a cohort of 26 Iranian patients with metastatic pancreatic cancer. Three genotypes were identified, including TTT/TTT (38%), TTT/T (54%), and T/T (8%). The overall survival of patients differed significantly according to genotype (log-rank p = 0.004). Patients carrying the homozygous T/T genotype experienced a markedly shorter mean overall survival (135 days) compared with individuals carrying the TTT/TTT (395 days) or TTT/T (450 days) genotypes. T/T genotype was associated with a substantially increased risk of death (HR = 8.14, 95% CI: 1.4–47.4). Consistent with these findings, recessive model analysis further confirmed that patients homozygous for the minor allele had significantly poorer survival than those carrying at least one TTT allele (log-rank p = 0.001; HR = 9.8, 95% CI: 1.8–54.4). Importantly, adjustment for age, sex, surgical intervention, and treatment regimen did not alter the association, suggesting that genotype independently influenced survival.
To explore whether SH3D21 variation also affected therapeutic response, patients were stratified according to gemcitabine treatment. Significant genotype-dependent differences in survival persisted in both gemcitabine-treated and non-gemcitabine-treated patients. Interestingly, the survival patterns differed between treatment groups. Among patients receiving gemcitabine, the heterozygous TTT/T genotype was associated with the most favorable outcome, whereas among patients treated primarily with 5-fluorouracil-based regimens, the TTT/TTT genotype demonstrated the longest survival. These observations suggest that rs34416442 may influence not only disease prognosis but also response to chemotherapy, supporting previous experimental evidence implicating SH3D21 in gemcitabine sensitivity.
This study provides the first clinical evidence linking SH3D21 rs34416442 with survival in pancreatic cancer patients. The findings identify the T/T genotype as a strong predictor of poor prognosis and suggest that the heterozygous genotype may derive greater benefit from gemcitabine-based treatment. These results indicate that SH3D21 rs34416442 has potential as a prognostic and predictive biomarker for precision management of pancreatic cancer.
You can read the full text of the article here: https://mbrc.shirazu.ac.ir/article_8676.html
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer because it is often diagnosed late, spreads rapidly, and responds poorly to current treatments. Although surgery, chemotherapy, and radiation remain the standard therapeutic options, their overall impact on long-term survival is limited. Consequently, there is growing interest in identifying natural compounds that could complement existing therapies. We investigated whether an ethanolic extract prepared from Cannabis sativa seeds possesses anti-cancer properties against the human pancreatic cancer cell line PANC-1.
Unlike most previous cannabis-related cancer studies, which focused on leaves or flowers rich in cannabinoids, this research examined the seeds. Cannabis seeds contain relatively low amounts of psychoactive THC but are rich in fatty acids, phytosterols, terpenes, antioxidants, and other bioactive compounds. Using GC-MS analysis, we identified eighteen major compounds in the extract. Fatty acids represented majority of the identified compounds, while cannabinoids such as cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), and cannabinol (CBN), together with phytosterols and terpenes, were also detected.
The biological activity of the extract was evaluated using several complementary laboratory assays. Cell viability experiments demonstrated that the seed extract inhibited the growth of PANC-1 pancreatic cancer cells in a concentration-dependent manner, with an IC₅₀ of approximately 1.3 mg/mL. Importantly, the same concentrations produced little or no inhibitory effect on normal human foreskin fibroblast (HFF) cells, suggesting a degree of selectivity toward cancer cells.
To determine whether the extract affected the clonogenic properties of cancer cells, colony formation assays were performed. Treatment significantly reduced the number of colonies formed and shifted colony morphology from highly proliferative holoclones toward less aggressive paraclones. This observation indicates a reduction in the tumor-forming potential of the treated cells.
We also investigated cancer cell migration using a wound-healing assay. Untreated PANC-1 cells nearly closed the artificial wound after 48 hours, whereas extract-treated cells migrated much more slowly, indicating that the extract suppresses cell motility. Since migration is a critical step in cancer invasion and metastasis, this finding suggests that the extract may reduce the metastatic potential of pancreatic cancer cells.
Flow cytometry provided insight into the underlying cellular mechanisms. The extract arrested a larger proportion of cells in the G1 phase of the cell cycle while decreasing the percentage of cells entering the S and G2/M phases. In addition, the proportion of sub-G1 cells increased, indicating enhanced apoptosis. Together, these findings show that the extract suppresses cancer cell proliferation by preventing cell-cycle progression and promoting apoptotic cell death.
Overall, this study provides the first evidence that Cannabis sativa seed extract possesses multiple anti-cancer activities against pancreatic cancer cells, including inhibition of proliferation, migration, and colony formation, together with induction of G1 cell-cycle arrest and apoptosis. Because the extract had minimal effects on normal fibroblast cells under the tested conditions, it may represent a promising candidate for future combination therapies.
You can read the full text of the article here: https://www.biorxiv.org/content/10.1101/2025.07.27.667016v1
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