The immunosuppressive tumor microenvironment has caused great obstacles to tumor immunotherapy, especially less tumor-associated antigens released from tumor sites. Herein, Ag2S QD/DOX/Bestatin@PC10ARGD genetically engineered polypeptide hydrogel PC10ARGD as sustained-release material...

There has been no consensus standard of care to treat recurrent cancer patients who have previously been irradiated. Pulsed low dose rate (PLDR) external beam radiotherapy has the potential to reduce normal tissue toxicities while still providing significant tumor control for recurrent cancers. This work investigates the dosimetry feasibility of PLDR treatment using dynamic arc delivery techniques. Five treatment sites were investigated in this study including breast, pancreas, prostate, head and neck, and lung. Dynamic arc plans were generated using the Varian Eclipse system and the RapidArc delivery technique with 6 and 10 MV photon beams. Each RapidArc plan consisted of two full arcs and the plan was delivered five times to achieve a daily dose of 200 cGy. The dosimetry requirement was to deliver approximately 20 cGy/arc with a 3 min interval to achieve an effective dose rate of 6.7 cGy min⁻¹. Monte Carlo simulations were performed to calculate the actual dose delivered to the planning target volume (PTV) per arc taking into account beam attenuation/scattering and intensity modulation. The maximum, minimum and mean doses to the PTV were analyzed together with the dose volume histograms and isodose distributions. The dose delivery for the five plans was validated using solid water phantoms inserted with an ionization chamber and film, and a cylindrical detector array. Two intensity-modulated arcs were used to efficiently deliver the PLDR plans that provided conformal dose distributions for treating complex recurrent cancers. For the five treatment sites, the mean PTV dose ranged from 18.9 to 22.6 cGy/arc. For breast, the minimum and maximum PTV dose was 8.3 and 35.2 cGy/arc, respectively. The PTV dose varied between 12.9 and 27.5 cGy/arc for pancreas, 12.6 and 28.3 cGy/arc for prostate, 12.1 and 30.4 cGy/arc for H&N, and 16.2 and 27.6 cGy/arc for lung. Advanced radiation therapy can provide superior target coverage and normal tissue sparing for PLDR reirradiation of recurrent cancers, which can be delivered using dynamic arc delivery techniques with ten full arcs and an effective dose rate of 6.7 ± 4.0 cGy min⁻¹.

The purpose of this study is to evaluate the treatment plan adequacy and delivery efficiency among volumetric-modulated arc therapy (VMAT) with one or two arcs and the conventional static-field dynamic multileaf collimator (dMLC) intensity-modulated radiation therapy (IMRT) in patients undergoing oropharyngeal carcinoma. Fifteen patient cases were included in this investigation. Each of the cases was planned using step-and-shoot IMRT, VMAT with a single arc (Arc1) and VMAT with double arcs (Arc2). A two-dose level prescription for planning target volumes (PTVs) was delivered with 70 Gy/56 Gy in 30 fractions. Comparisons were performed of the dose-volume histograms (DVH) for PTVs, the DVH for organs at risk (OARs), the monitor units per fraction (MU/fx), and delivery time. IMRT and Arc2 achieved similar target coverage, but superior to Arc1. Apart from the oral cavity, Arc1 showed no advantage in sparing of OARs compared with IMRT, while Arc2 obtained equivalent or better sparing of OARs among the three techniques. VMAT reduced MU/fx and shortened delivery time remarkably compared with IMRT. Our results demonstrated that for oropharyngeal cases, Arc2 can achieve superior target coverage and normal tissue sparing, as well as a significant reduction in treatment time.

Abstract. Progestin and adipoQ receptor family member III (PAQR3) is a regulator that negatively modulates the Ras/Raf/ MEK/ERK signaling cascade and the GPCR Gβγ subunit signaling pathway. The role of PAQR3 in hepatocellular carcinoma (HCC) has not been elucidated. The present study investigated the expression of PAQR3 and its prognostic value in primary HCC patients. Furthermore, the functional aspects of PAQR3 were also studied using an in vitro cell model. PAQR3 expression was examined in paired HCC and adjacent noncancerous tissues using real-time quantitative RT-PCR (62 pairs) and western blotting (26 pairs). We also analyzed PAQR3 expression in 132 additional HCC samples by immunohistochemistry. The functional impact of PAQR3 on the proliferation and colony formation of an HCC cell line was analyzed by transfecting cells with a full-length PAQR3 expression vector or siRNA targeting PAQR3. The expression of PAQR3 was significantly decreased in the cancer tissues. Clinicopathological analyses showed that the expression of PAQR3 was significantly correlated with expression of serum α-fetoprotein (AFP), mitotic count, tumor size, histological grade and recurrence. Notably, Kaplan-Meier survival curves revealed a correlation between decreased expression of PAQR3 and the poor prognosis of HCC patients. Multivariate analyses showed that PAQR3 expression is an independent prognostic marker for overall and disease-free survival of HCC patients. Furthermore, restoring PAQR3 expression in HCC cells significantly diminished Hep3B cell proliferation and colony formation. Silencing PAQR3 expression in hepatic normal cell line LO2 significantly enhanced cell growth. PAQR3 may play an important role in the progression of HCC and serve as a potential candidate for the targeted therapy of HCC.