Preliminary response to Tislelizumab plus chemotherapy drugs in patient with periampullary carcinoma: a report of one case and a literature review.

Periampullary carcinoma is a malignant gastrointestinal tumor originating from the head of the pancreas, distal bile duct, duodenum, or the ampulla of Vater. Currently, surgery remains the primary treatment option, yet the postoperative recurrence rate remains high. Chemotherapy is the main approach for controlling postoperative recurrence. Histologically, periampullary carcinoma is categorized into two types: intestinal (IN) and pancreaticobiliary (PB) subtype. Each subtype requires different therapeutic approaches, with the PB type primarily treated with gemcitabine and the IN type with 5-FU. Despite these options, patient outcomes are still unsatisfactory. In recent years, the feasibility of immunotherapy in tumor treatment has been increasingly evidenced, although research on its efficacy in periampullary carcinoma treatment is still limited. In this report, we present a case of a periampullary carcinoma patient who experienced recurrence and metastasis after undergoing radical pancreatoduodenectomy and receiving gemcitabine-based chemotherapy post-surgery. Through next-generation sequencing (NGS), we identified high expression levels of programmed cell death-ligand 1 (PD-L1) with a combined positive score (CPS) of 35, high tumor mutation burden (TMB-H), and high microsatellite instability (MSI-H) in this patient. Therefore, we implemented a combination therapy using Tislelizumab and chemotherapy. According to the latest follow-up, the tumors are effectively controlled. Our utilization of immunotherapy combined with chemotherapy holds significant implication for the treatment of periampullary carcinoma.

Customizable Zr-MOF nanoantidote-based multieffective arsenic detoxification and its extended low-toxic therapy.

Arsenic (As) poisoning has become a global public problem threatening human health. Chelation therapy (CT) is the preferred treatment for arsenic poisoning. Nevertheless, efficient and safe arsenic removal in vivo remains a daunting challenge due to the limitations of chelators, including weak affinity, poor cell membrane penetration, and short half-life. Herein, a mercapto-functionalized and size-tunable hierarchical porous Zr-MOF (UiO-66-TC-SH) is developed, which possesses abundant arsenic chemisorption sites, effective cell uptake ability, and long half-life, thereby efficiently removing toxic arsenic in vivo. Moreover, the strong binding affinity of UiO-66-TC-SH for arsenic reduces systemic toxicity caused by off-target effects. In animal trials, UiO-66-TC-SH decreases the blood arsenic levels of acute arsenic poisoning mice to a normal value within 48 h, and the efficacy is superior to clinical drugs 2,3-dimercaptopropanesulfonic acid sodium salt (DMPS). Meanwhile, UiO-66-TC-SH also significantly mitigates the arsenic accumulation in the metabolic organs of chronic arsenic poisoning mice. Surprisingly, UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates the side effects of arsenic drugs antitumor therapy. STATEMENT OF SIGNIFICANCE: Arsenic (As) contamination has become a global problem threatening public health. The present clinical chelation therapy (CT) still has some limitations, including the weak affinity, poor cell membrane permeability and short half-life of hydrophilic chelators. Herein, a metal-organic framework (MOF)-based multieffective arsenic removal strategy in vivo is proposed for the first time. Mercapto-functionalized and size-tunable hierarchical porous Zr-MOF nanoantidote (denoted as UiO-66-TC-SH) is accordingly designed and synthesized. After injection, UiO-66-TC-SH can form Zr-O-As bonds and As-S bonds with arsenic, thus enhancing arsenic adsorption capacity, cycling stability and systemic safety simultaneously. The acute arsenic poisoning model results indicate that UiO-66-TC-SH shows superior efficacy to the clinical drug sodium dimercaptopropanesulfonate (DMPS). More meaningfully, we find that UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates side effects of arsenic drugs anti-tumor therapy.