Phospholipase A and acyltransferase 4/retinoic acid receptor responder 3 at the intersection of tumor suppression and pathogen restriction.

Phospholipase A and acyltransferase (PLAAT) 4 is a class II tumor suppressor with phospholipid metabolizing abilities. It was characterized in late 2000s, and has since been referred to as 'tazarotene-induced gene 3' (TIG3) or 'retinoic acid receptor responder 3' (RARRES3) as a key downstream effector of retinoic acid signaling. Two decades of research have revealed the complexity of its function and regulatory roles in suppressing tumorigenesis. However, more recent findings have also identified PLAAT4 as a key anti-microbial effector enzyme acting downstream of interferon regulatory factor 1 (IRF1) and interferons (IFNs), favoring protection from virus and parasite infections. Unveiling the molecular mechanisms underlying its action may thus open new therapeutic avenues for the treatment of both cancer and infectious diseases. Herein, we aim to summarize a brief history of PLAAT4 discovery, its transcriptional regulation, and the potential mechanisms in tumor prevention and anti-pathogen defense, and discuss potential future directions of PLAAT4 research toward the development of therapeutic approaches targeting this enzyme with pleiotropic functions.

Chinese Expert Consensus on Iodine125 Seed Implantation for Recurrent Cervical Cancer in 2021.

The treatment modality for recurrent cervical cancer (rCC) is limited, and the prognosis of these patients is poor. Seed implantation could be an important component of rCC management in the context of dose boost or salvage therapy after surgery or radiotherapy, which is characterized by a minimally invasive, high local dose, and rapidly does fall, sparing normal tissue. For patients with good performance status and lateral pelvic wall recurrence with an available puncture path, seed implantation was recommended, as well as for selected central pelvic recurrence and extra-pelvic recurrence. The combination of brachytherapy treatment planning system and CT guidance was needed, and three-dimensional printing templates could greatly improve the accuracy, efficiency, and quality of seed implantation to achieve a potential ablative effect and provide an efficient treatment for rCC. However, the recommendations of seed implantation were mainly based on retrospective articles and lack high-quality evidence, and multicenter prospective randomized studies are needed. In this consensus on iodine125 seed implantation for rCC, indication selection, technical process and requirements, dosimetry criteria, radiation protection, combined systemic therapy, and outcomes of seed implantation for rCC are discussed.

Dosimetry comparison between a 3D printed minimally invasive guidance template and free implantation in the brachytherapy treatment of postoperative recurrent cervical carcinoma.

Objective: This study aimed to investigate the dosimetry difference between a 3D printed minimally invasive guidance template and conventional free implantation in brachytherapy of postoperative recurrent cervical carcinoma under the guidance of computed tomography (CT). Methods: A total of 21 cases of patients with recurrent cervical cancer after operation were enrolled from January 2017 to June 2018. After external irradiation treatment in 1.8-Gy fractions to 45 Gy, patients were randomly divided into two groups to receive brachytherapy: 11 cases were assisted by a 3D-printed minimally invasive guidance template, and the other 10 cases were free implantation. In the template group, needles were inserted according to the main guide channel of the template commissioned in medical photosensitive resin, while patients in the other group were treated with bare hands under the guidance of CT, which was used in both groups to adjust the position and depth of the implant needles. After transmission of the CT images into the Oncentra® Brachy TPS system, the target organs and organs at risk were delineated for further treatment. Results: The D90 value of the high-risk clinical target volume in the template group was 6.30±0.21 Gy while that in the other group was 6.07±0.32 Gy (P<0.05). In addition, the D2cm3 (illuminated dose of 2 cm3 of organ at risk) value of the bladder, rectum, sigmoid colon, and bowel was significantly decreased in the template group as compared to the free group (P<0.05). The number of needles used for each treatment in the template group was 5.71±1.82, while that for the free injection group was 7.78±2.35 (P<0.05). Conclusion: Compared with conventional free implantation, the 3D printed minimally invasive guidance template-assisted treatment has an obvious dosimetry advantage in the treatment of postoperative recurrent cervical carcinoma, with shorter time of implantation and better repeatability.

Indication of Bevacizumab for Cerebral Radiation Necrosis.

BACKGROUND: The effect of bevacizumab (BVZ) for Cerebral Radiation Necrosis (CRN) was clear. However, the indications of BVZ had no reports. OBJECTIVE: The aim of the paper was to investigate the indications of BVZ for CRN. METHODS: Fourteen CRN patients (confirmed by imaging diagnosis) who underwent BVZ treatment between June 2011 and December 2014 were analyzed. BVZ was administered (5mg/kg body weight) once every three to four weeks for at least three cycles. Contrast-enhanced T1 MRI signal intensity changes were measured after BVZ treatment, to evaluate the clinical efficacy of BVZ and the recurrence and progression of CRN. Three patients who were followed for a longer duration were described in detail. The main observations included the indications and (the) use of BVZ for CRN. RESULTS: Most patients undergoing BVZ treatment for CRN exhibited recurrence. One of the three patients described in detail was asymptomatic; CRN was reduced but then progressed, and a second course of BVZ failed. The other two patients showed obvious symptoms of primary CRN; CRN was significantly reduced, but then progressed with mild symptoms. A second short course of BVZ showed poor efficacy in one patient who demonstrated long-term stability after BVZ withdrawal. Second long course of BVZ resulted in further aggravation of CRN in the other patient, and a re-examination revealed spontaneous remission of CRN. CONCLUSION: Symptoms are an indication of BVZ treatment for primary CRN.

miR-297 acts as an oncogene by targeting GPC5 in lung adenocarcinoma.

OBJECTIVES: Emerging studies have demonstrated that microRNAs (miRNAs) play crucial roles in carcinogenesis of many developing human tumours. However, the functions and mechanisms of miR-297 in lung cancer have, up to now, been largely undefined. MATERIALS AND METHODS: Here, miR-297 expression was measured in lung adenocarcinoma tissues and cell lines, using qRT-PCR. Lung adenocarcinoma cell line was treated with an miR-297 mimic. MTT and colony analysis were performed to detect cell proliferation and colony formation. The direct target gene of miR-297 was assessed by qRT-PCR, Western blotting and luciferase assays. RESULTS: We demonstrated that miR-297 expression was upregulated in lung adenocarcinomas compared to adjacent normal tissues. Expression of miR-297 was also upregulated in tested lung adenocarcinoma cell lines. Ectopic expression of miR-297 enhanced lung adenocarcinoma cell proliferation and colony formation. Furthermore, overexpression of miR-297 promoted cell migration and invasion. In addition, we identified Glypican-5 (GPC5) as a direct target gene of miR-297 in lung adenocarcinoma cells. Expression of GPC5 was downregulated in both lung adenocarcinoma tissues and cell lines. Moreover, expression of GPC5 was inversely associated with expression of miR-297 in lung adenocarcinoma tissues. CONCLUSIONS: These results suggest that miR-297 acted as an oncogenic miRNA, partly by targeting GPC5, adenocarcinoma of the lung.

A study on the evaluation method and recent clinical efficacy of bevacizumab on the treatment of radiation cerebral necrosis.

In order to investigate the efficacy of bevacizumab on the treatment of radiation cerebral necrosis, patients who were diagnosed with radiation cerebral necrosis by imaging after stereotactic radiotherapy were collected. Bevacizumab was applied at a dose of 5 mg/kg once every three weeks at least three times. The changes in cerebral necrosis symptoms before and after treatment, the cerebral edema volume, the cerebral necrosis volume, and the changes in magnetic resonance imaging (MRI) strengthening phase signals of cerebral necrosis were used as the first observation point. The side effects of bevacizumab were used as the second observation point. Total of 14 radiation cerebral necrosis patients were treated with bevacizumab between June 2011 and February 2013 were collected. There were 12 symptomatic patients, of whom 10 patients (83.3%) had reduced symptoms. The edema index grades of nine patients (64.29%) improved. The cerebral necrosis volumes of 13 patients (92.86%) decreased. The T1 phase signal strengths of the intracranial enhanced MRIs of 12 patients (85.71%) significantly decreased. The clinical side effects of bevacizumab were mild. In conclusion, Preliminary results showed that treatment of radiation cerebral necrosis using bevacizumab was safe and effective. This treatment measure is worthy of further study.

Acquired-resistance of bevacizumab treatment for radiation brain necrosis: a case report.

The case study reported on acquired bevacizumab resistance in one patient receiving re-treatment with bevacizumab following radiation brain necrosis progression after bevacizumab was discontinued. This case offers novel and additional insight for bevacizumab treatment. Low-dose bevacizumab is effective for radiation brain necrosis, and radiation brain necrosis may progress after bevacizumab discontinuation, whereas too many cycles of bevacizumab treatment may induce drug-resistance and re-treatment failure following the progression. Therefore, more rational administration for radiation brain necrosis with bevacizumab may include three aspects: short-course treatment, timely discontinuation upon obtaining satisfactory effects (to prevent long-term medication associated resistance) and re-treatment after brain necrosis progression.

Exploration of the recurrence in radiation brain necrosis after bevacizumab discontinuation.

OBJECTIVE: The aim of the paper was to investigate the recurrence and its causes of radiation brain necrosis following bevacizumab discontinuation. METHODS: This study included 14 patients with radiation brain necrosis (confirmed through imaging) after stereotactic radiotherapy for a primary or metastatic brain tumor and who received bevacizumab treatment from June 2011 through December 2014. The patients received bevacizumab at 5 mg/kg, q3-4w, for at least 3 cycles. The T1 signal intensity from enhanced MRI images was used as the evaluation criteria for the brain necrosis treatment efficacy. RESULTS: brain necrosis improved in 13 of the 14 cases (92.9%). However, during follow-up, 10 of the 13 responsive patients (76.9%) exhibited a recurrence in brain necrosis, and a multiple linear regression analysis shows that brain necrosis recurrence was related to the follow-up time after the initial bevacizumab treatment discontinuation. CONCLUSION: bevacizumab produced good short-term effects for radiation brain necrosis; however, most of the patients would recurrence after bevacizumab is discontinued. Thus, brain necrosis was irreversible.