In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that predominantly affects women of reproductive age. Risk of SLE flare during pregnancy is dependent on disease activity of SLE and proteinuria at the time of conception, which affect pregnancy outcome. We report on three patients who developed renal flares during pregnancy after remission of lupus nephritis before pregnancy. Two patients were treated successfully, with pregnancy outcomes of live births however, another patient's pregnancy was terminated with induced abortion. For SLE patients, family planningis needed until disease activity of SLE has been stable for at least six months prior to the pregnancy. Nevertheless, flares of lupus could develop and influence maternal and fetal outcome. Therefore, renal flares during pregnancy should be recognized and treated immediately.
Abortion, Induced ; Female ; Fertilization ; Humans ; Live Birth ; Lupus Erythematosus, Systemic ; Lupus Nephritis* ; Nephritis ; Pregnancy ; Pregnancy Outcome ; Pregnant Women* ; Proteinuria

Despite the increasing use of the rectal balloon in prostate cancer radiotherapy, many issues still remain to be verified objectively including its positional reproducibility and relevance to treatment morbidity. We have developed a custom rectal balloon that has a scale indicating the depth of insertion and dilates symmetrically ensuring positional reproducibility. Fifty patients with prostate cancer treated by definitive 3D-conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) with rectal balloon were analyzed. Each of first five patients undergone computed tomography (CT) three times with a rectal balloon. The positional reproducibility was tested by Intraclass Correlation Coefficient (ICC) from the CT-to-CT fusion images. Planning variables and clinical acute toxicities were compared between when or not applying balloon. An ICC of greater than 0.9 in all directions revealed an excellent reproducibility of the balloon. Rectal balloon improved considerably the mean dose and V(45Gy)-V(65Gy) in plan comparison, and especially in 3D-CRT the rectal volume exposed to more than 60 Gy dropped from 41.3% to 19.5%. Clinically, the balloon lowered acute toxicity, which was lowest when both the balloon and IMRT were applied simultaneously. The rectal balloon carries excellent reproducibility and reduces acute toxicity in 3D-CRT and IMRT for prostate cancer.
Balloon Dilatation/*methods ; Dose-Response Relationship, Radiation ; Humans ; Male ; Neoplasm Staging ; Prostatic Neoplasms/*radiotherapy ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated ; *Rectum ; Tomography, X-Ray Computed ; Treatment Outcome