Background: Surgery remains the mainstay treatment for solid cancers. Whether cancer should be regarded as a systemic disease and the role that surgery plays beyond local tumor removal remains unresolved.

Methods: We evaluated the pathological TNM (pTNM) status (pTis-T2/T3N0M0 vs. pTisT4N1/M1_a: all except pTis-T2/3N0M0, and pTisT1N0M0 vs. pTis-T4N1/M1_b, all except pTis-T1N0M0 patients) of 1,775 patients with histologically confirmed adenocarcinoma without multiple primary malignancies, gastric lymphoma, or unknown pathology who underwent human leukocyte antigen (HLA) testing. After resection surgery (RS), the patients received fluoropyrimidine antimetabolites (FA), polysaccharide K (PSK), mitomycin C (MMC), or their combinations (FPSK, MF, and MFPSK). Based on previously identified HLA profiles associated with favorable or detrimental survival, patients were classified as predicted responders (Good) or non-responders (Poor) to RS only and each postoperative adjuvant therapy. Overall survival was analyzed according to pTNM status, sex, age, and family history (FH).

Results: Survival outcomes varied according to HLA-defined good or poor status, sex, FH, and pTNM status. In organ-confined tumors (pTis–T1N0M0 or pTis–T2/3N0M0), men with Good-RS without FH and those in FH group E had significantly improved survival with RS only, whereas patients with Poor-RS had significantly worse outcomes. In advanced disease (pTis–T4N1/M1_a), Good-MFPSK men without FH and Poor-PSK patients in FH group A, and in pTis-T4N1/M1_b, Good-MMC patients in FH group H had a significant survival benefit.

Conclusions: These findings highlight the limitations of RS alone but suggest that tumor removal may improve immunosuppression in selected patients. HLA-based responder/non-responder classification may support individualized therapeutic decision-making.

Introduction: Tick salivary glands constitute a largely untapped reservoir of bioactive molecules with significant therapeutic potential. Here, we investigated the selective anticancer activity of salivary gland extract (SGE) from the tortoise tick Hyalomma aegyptium using cancer cell line, non-tumorigenic cells, and primary human tissue cultures.

Methods: The effects of Hyalomma aegyptium salivary gland extract (SGE; 200–600 ng protein/mL) on HeLa cells, HEK293T cells, and primary human chondrocyte and annulus fibrosus/nucleus pulposus (AF/NP) cell cultures were evaluated after 24 h of treatment. Cell viability, proliferation, and morphology were assessed using MTT assay, acridine orange/propidium iodide (AO/PI) staining, and microscopic analysis.

Results: SGE induced a dose-dependent reduction in viability in HeLa cells. In HeLa cells, SGE treatment (200–600 ng protein/mL, 24 h) reduced cell viability by 46.1–65.9% in a concentration-dependent manner while exerting minimal suppressive effects on AF/NPc. Chondrocyte and HEK293T cell viability increased by up to 29.9% and 125.0% of the control level, respectively.

Conclusion: The results suggest that SGE exerts a stronger inhibitory effect on HeLa cells at exceptionally low protein concentrations, supporting its potential as a source of novel anticancer molecules. Further fractionation and mechanistic studies are warranted to identify the active molecules, clarify their mechanisms of action, and determine whether they possess true tumor-targeted activity.