The role of autophagy in the treatment of colon cancer by chlorin e6 photodynamic therapy combined with oxaliplatin.

BACKGROUND: Photodynamic therapy is a tumour treatment method. Its mechanism mainly induces apoptosis, autophagy, and other ways to cause cell death. Therefore, this study aims to evaluate the therapeutic effect of chlorine e6 photodynamic therapy (Ce6-PDT) combined with oxaliplatin (L-OHP) in colon cancer and to investigate the role of autophagy in L-OHP treatment and Ce6-PDT combined with L-OHP in colon cancer. METHODS: CCK-8 assay, Scratch wound healing assay, and Western Blot (WB) were used to identify drug-resistant colon cancer cell line SW620/L-OHP. Annexin V/FITC assay, laser confocal double immunofluorescence staining method and WB were employed to investigate the apoptosis and autophagy changes in Ce6-PDT combined with L-OHP. RESULTS: Drug resistance cells SW620/L-OHP were developed under the continuous multi-generation of L-OHP treatment, and the expression of ATP-binding cassette subfamily B member 1 (ABCB1) and ATG5 proteins were increased. The results of immunofluorescence showed that LC3B accumulated in SW620 cells and SW620/L-OHP cells under the treatment of L-OHP. The WB results indicated that LC3B and ATG5 protein expression was increasing in SW620 cells and SW620/L-OHP cells. Inhibition of L-OHP-induced autophagy reduces SW620 cells and SW620/L-OHP cells' viability while increasing apoptosis and the Pro Caspase-3 protein expression. The combination of Ce6-PDT and L-OHP decreased the cell viability, the cell migration ability, the Bcl-2 protein expression, and increased the apoptosis rate, Pro Caspase-3 protein expression in SW620 cells. CONCLUSIONS: L-OHP can cause SW620 cells drug resistance. Autophagy plays a protective role in the L-OHP treatment of SW620 cells and SW620/L-OHP cells, and inhibition of autophagy can increase the efficacy of L-OHP. Ce6-PDT combined with L-OHP can further improve the tumor's therapeutic effect, and autophagy inhibition can improve the efficacy of combined therapy.

The utility of diffusion-weighted imaging and ADC values in the characterization of mumps orchitis and seminoma.

BACKGROUND: Diffusion-weighted imaging (DWI) can quantitatively reflect the diffusion characteristics of tissues, providing a theoretical basis for qualitative diagnosis and quantitative analysis of a disease. PURPOSE: To characterize testicular lesions that present as a hypointense signal on magnetic resonance imaging (MRI) T2-weighted images using DWI. MATERIAL AND METHODS: Study participants were divided into three groups. Group A were healthy controls (n = 35), group B included patients with mumps orchitis (n = 20), and group C included patients with seminoma (n = 15). DWI sequences used b-values of 0, 1000, and 2000 s/mm2. Apparent diffusion coefficient (ADC) values between 1000 and 2000 s/mm2 were calculated by MRI postprocessing software. The Kruskal-Wallis test and receiver operating characteristic analysis were performed to evaluate how well ADC values distinguished between mumps orchitis and seminoma. RESULTS: Normal testicular tissue showed a hyperintense signal on DWI and hypointensity on the ADC map: mean ADC value was 0.77 (0.69-0.85) ± 0.08 ×10-3 mm2/s. Mumps orchitis and seminoma showed slight hyperintensity on DWI: mean ADC values were 0.85 (0.71-0.99) ± 0.15 ×10-3 mm2/s and 0.43 (0.39-0.47) ± 0.04 × 10-3 mm2/s, respectively. There were statistically significant differences in mean ADC values between normal testicular tissue and seminoma and between mumps orchitis and seminoma. The cutoff ADC value for differentiating seminoma from mumps orchitis was 0.54 × 10-3 mm2/s. The sensitivity, specificity, and Youden Index for diagnosing seminoma were 99%, 31%, and 30%, respectively. CONCLUSION: High b-value DWI has potential utility for differentiating mumps orchitis from seminoma in the clinical setting.

MRI findings of an atypical testicular epidermoid cyst: A case report.

INTRODUCTION: Typical testicular epidermoid cysts (TECs) manifestate as a target sign or onion skin sign on ultrasonography and magnetic resonance (MR) imaging. Clinicians are increasingly aware of the imaging characteristics of typical TECs, which allow accurate diagnosis and successful treatment while preserving the testicle, but atypical TECs are likely to be misdiagnosed as a malignant intratesticular neoplasm, leading to complete testicular resection. PATIENT CONCERNS: A 26 year-old male patient complained of a painless enlargement of the left testicle that had been present for 1 month. The patient had no recent medical history of scrotal trauma or systemic infection. DIAGNOSIS: A round 48 mm × 45 mm × 43 mm mass was seen inside the left testicle. T2-weighted images of the lesion showed a thin hypointense capsule. T1-weighted images of the lesion showed a hyperintense nodule on the cyst wall, which appeared hypointense on T2-weighted and SPAIR images. After Gd-DTPA injection, the lesion was not enhanced; however, the nodule was enhanced on THRIVE images. These manifestations were consistent with a benign intratesticular lesion, and MR imaging diagnosed atypical TEC, which was confirmed by pathology after surgery. INTERVENTIONS: The patient was treated with organ-sparing surgery with testicular enucleation. OUTCOMES: The patient was re-examined with ultrasonography 3 months after surgery. The left residual testicular tissue appeared normal, and reproductive function was preserved. CONCLUSION: Urologists must be aware of the clinical and MR imaging characteristics of atypical TECs and the utility of preoperative MR imaging for the diagnosis of testicular lesions to ensure that organ-sparing surgery is performed rather than unnecessary orchiectomy.

Improving radio-chemotherapy efficacy of prostate cancer by co-deliverying docetaxel and dbait with biodegradable nanoparticles.

Combining DNA damage repair inhibitors and chemotherapeutic agents is an emerging strategy in cancer treatment. In this study, we engineered the polycation nanoparticle (NP), which co-encapsulated DNA damage repair inhibitor Dbait and chemotherapeutic drug Docetaxel (Dtxl), using H1 nanopolymer (folate--polyethylenimine600-cyclodextrin), and the size of H1/Dbait/Dtxl was about 117 nm. We demonstrated that H1/Dbait/Dtxl enhanced the efficiency of radio-chemotherapy in prostate cancer cells by CCK-8 assay and colony-forming assay. Importantly, the improvement of radio-chemotherapy of H1/Dbait/Dtxl in prostate cancer was also validated in vivo, and the NP did not have a high toxicity profile. The results of immunohistochemistry and western blot supported that the improved therapeutic efficacy was through inhibiting DNA damage repair signalling pathway. Our study supports further investigations using NP to co-deliver DNA damage repair inhibitors and chemotherapeutics to improve the therapeutic efficacy of cancer.

Differentiation of testicular seminoma and nonseminomatous germ cell tumor on magnetic resonance imaging.

Magnetic resonance imaging (MRI) has excellent soft tissue resolution, as well as multidirectional and multisequence scanning technology, making it an important supplementary method in the diagnosis of testicular tumor.To explore the utility of preoperative MRI for the differential diagnosis of testicular seminoma and nonseminomatous germ cell tumors (NSGCTs).The medical records from 39 patients with testicular tumors that were examined preoperatively with MRI and treated with urologic surgery at our institution between January 2015 and March 2019 were retrospectively reviewed. Testicular tumors were confirmed by pathology and classified as seminoma (n = 20) or NSGCT (n = 19). Two radiologists analyzed the testicular tumors on preoperative MRI for morphology: multiple nodules or a single mass; presence/absence of a capsule; signal compared to the normal contralateral testicle (isointense, hypointense, hyperintense, or mixed); enhancement; septa; and hemorrhagic or cystic degeneration. Characteristics of seminomas and NSGCT were compared using the Chi-square or Fischer exact test.MRI showed that the majority (95%; 19/20) of seminomas were nodular. There were significant differences in the presence/absence of a capsule (P = .001), T1-weighted imaging (T1WI) signal intensity (P = .047), T2-weighted imaging (T2WI) signal intensity (P < .001), septa (P < .001), and hemorrhagic or cystic degeneration (P < .001) between seminomas and NSGCT.Seminomas were more likely to have no capsule, isointensity on T1WI, hypointensity on T2WI, and had narrow obviously enhanced fibrovascular septa without hemorrhagic or cystic degeneration; NSGCT was more likely to have a capsule, a mainly mixed signal on T1WI and T2WI, most of them had no fibrovascular septa, and hemorrhagic or cystic degeneration was common in malignant NSGCT.This study suggests that preoperative MRI can distinguish seminoma from NSGCT. We propose that preoperative MRI of the scrotum is an effective technique that should be widely adopted for the management of scrotal disease.

The Efficacy and Safety of Iodine-125 Brachytherapy Combined with Chemotherapy in Treatment of Advanced Lung Cancer: A Meta-Analysis.

The aim of this study was to systematically review the efficacy and safety of iodine-125 brachytherapy combined with chemotherapy in patients with advanced lung cancer. PubMed, MEDLINE, EBSCO, FMJS and Web of Science were searched to obtain randomized controlled trials (RCTs), published in English and Chinese, until February 2016. The evaluating indicators were complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), overall response rate (ORR), disease control rate (DCR), one-year overall survival, two-year overall survival and adverse events. Revman 5.2 software was used for data syntheses and analyses. A total of 296 patients enrolled in 5 RCTs were ultimately included in this study based on our selection criteria, and 150 patients received chemotherapy alone, while another 146 patients received the combination therapy of iodine-125 brachytherapy and chemotherapy. The results showed that iodine-125 brachytherapy combined with chemotherapy was superior to chemotherapy alone in CR (risk ratio [RR] = 3.66, 95% confidence interval [CI]: 2.08 to 6.44, p<0.001), PR (RR = 1.47, 95% CI: 1.16 to 1.86, p=0.001), ORR (RR = 1.85, 95% CI: 1.54 to 2.22, p<0.001), DCR (RR = 1.19, 95% CI: 1.10 to 1.29, p<0.001), one-year overall survival (RR = 1.46, 95% CI: 1.12 to 1.92, p=0.006) and PD (RR = 0.20, 95% CI: 0.09 to 0.43, p<0.001); meanwhile, there was no significant difference in two-year overall survival (RR = 1.30, 95% CI: 0.72 to 2.37, p=0.39). In terms of adverse events, the combination therapy significantly increased the incidence of neumothorax (RR = 4.93, 95% CI: 1.94 to 12.55, p=<0.001); however, no significant differences were found in the incidence of other adverse events. This study indicated that the combination therapy of iodine-125 brachytherapy and chemotherapy could improve the therapeutic efficacy of advanced lung cancer without increasing the incidence of adverse events, except pneumothorax.

Folate-targeted nanoparticle delivery of androgen receptor shRNA enhances the sensitivity of hormone-independent prostate cancer to radiotherapy.

Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa). PCa patients typically receive androgen deprivation therapy; nonetheless, these patients eventually develop castration and radiation resistance. We hypothesized that we could further improve radiotherapeutic efficacy of hormone-independent PCa (HIPC) by silencing AR. In this study, nanoparticle (NP) AR-shRNA was formulated using folate-targeted H1 nanopolymer. We demonstrated that NP AR-shRNA enhances PCa radiosensitivity as indicated by the inhibition of cell growth, increased apoptosis, and increased cell cycle arrest in AR-dependent HIPC in vitro. The radiosensitizing effect of NP AR-shRNA could be validated in vivo, as NP AR-shRNA significantly suppressed tumor growth and prolonged the survival of HIPC tumor-bearing mice. Analysis at the molecular level revealed that NP AR-shRNA inhibits DNA damage repair signaling pathways. Our study supports further investigation of NP AR-shRNA for the improvement of radiotherapy efficacy in HIPC.

Hypoxia stimulates invasion and migration of human cervical cancer cell lines HeLa/SiHa through the Rab11 trafficking of integrin αvß3/FAK/PI3K pathway-mediated Rac1 activation.

Hypoxia plays a key role in tumour cell survival, invasion, and metastasis. An increasing number of studies have attempted to characterize the tumour response to hypoxia and to identify predictive markers of disease. Here we show that hypoxia increases tumour cell invasion and migration by the modulation of Rab11, an important molecule for vesicular trafficking. In our study, we found that Rab11, together with the activation of Rac1, could stimulate invasion and migration of cervical cancer cell lines HeLa/SiHa in hypoxia. Activation of Rac1 activity by hypoxia seems to be central to carcinoma invasion. We also found that these effects could be related to the integrin αvß3. In addition, we studied the molecular pathway for this process. Our results showed that in cervical cancer cell lines HeLa/SiHa, Rac1 activation in hypoxia could stimulate invasion and migration, and this process was mediated by integrin αvß3-mediated FAK and PI3K phosphorylation. Furthermore, hypoxia induced a dramatic increase in αvß3 integrin surface expression, and this increase is dependent on Rab11. In conclusion, our study might provide a new mechanism for the effect of hypoxia on stimulating cervical carcinoma invasion.