Baseline anemia predicts a poor prognosis in patients with non-small cell lung cancer with epidermal growth factor receptor mutations: a retrospective study.

BACKGROUND: Anemia is relatively common in cancer patients, and baseline anemia is associated with poor survival in patients with non-small cell lung cancer (NSCLC). However, there is a lack of large-sample studies of patients with NSCLC with epidermal growth factor receptor (EGFR) mutations. METHODS: We retrospectively analyzed anemia­related data for patients with NSCLC and EGFR mutations who were admitted to Zhejiang Cancer Hospital from January 2013 to June 2019 and treated with targeted therapy. The patients' clinicopathological features were evaluated by χ2 tests and the relationships between clinical characteristics and prognosis were investigated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 2,029 patients treated with EGFR-tyrosine kinase inhibitors (TKIs) were finally enrolled in this study, of whom 24.6% had baseline anemia. Patients without baseline anemia had longer median overall survival (OS) than patients with baseline anemia (36.10 vs. 29.10 months, P = 0.001), and patients with grade < 2 anemia had longer median OS than those with grade ≥ 2 anemia (35.00 vs. 25.10 months, P < 0.001). Multivariate analyses identified baseline anemia as a factor predicting a poor prognosis in terms of OS in patients with EGFR mutations. CONCLUSIONS: Baseline anemia is a significant factor predicting a poor prognosis in terms of OS in patients with NSCLC and EGFR mutations treated with targeted therapy. A higher grade of baseline anemia may also be related to shorter OS. And a higher risk of EGFR-mutated patients who had received targeted therapy could also be observed.

[Double-mutated oncolytic adenovirus combined with gemcitabine for treating an orthotopic nude mouse model of bladder cancer].

OBJECTIVE: To investigate the therapeutic efficacy of double-mutated oncolytic adenovirus AxdAdB-3 in combination with gemcitabine for treating bladder cancer in an orthotopic nude mouse model. METHODS: The susceptibility to the adenovirus was evaluated in bladder cancer cell lines YTS-1, T24, 5637 and KK47, and normal cell lines HCV29 and WI38. The cells were infected with AxCAlacZ and stained with 5-bromo-4-chloro-3-indolyl-ß-galactoside (X-Gal). Immunostaining against adenoviral hexon protein was performed to determine the selective replication of AxdAdB-3 in the cancer cells. Flow cytometry was used to determine the YTS-1 cells in S phase of cell cycle after adenovirus infection. Cell viability after AxdAdB-3 and/or gemcitabine was measured by CCK-8 assay. Orthotopic bladder cancer model was established in nude mice, and the inhibitory efficacy of intravesical instillation therapy with AxdAdB-3 or/and gemcitabine was assessed. RESULTS: Gene transduction efficiency was different among the cell lines, and correlated with expression of CAR. 5637 and KK47 cells with high expression of CAR were more susceptible to the adenovirus, whereas YTS-1 and T24 cells with little CAR expression were resistant to adenoviral infection. Immunostaining showed that the expression levels of hexon protein varied among the cell lines. Normal cells infected with AxdAdB-3 expressed little hexon protein. The proportion of S-phase cells was (39 ± 3) % and (49 ± 5) % in the AxCAlacZ- and AxdAdB-3-infected bladder cancer cells, respectively. AxdAdB-3 effectively induced S-phase entry of cell cycle (P < 0.05). AxdAdB-3 combined with gemcitabine significantly inhibited the growth of bladder cancer cell lines. In vivo, the mean weight of the bladder tumors in mice treated with intravesical instillation of AxCAlacZ, gemcitabine, AxdAdB-3, and AxdAdB-3 + gemcitabine were 400.6, 126.4, 82. 0, 40.4 mg, respectively. Either AxdAdB-3 (P < 0.0001) and gemcitabine (P < 0.0001) suppressed the tumor growth in nude mice, and the combination therapy reduced tumors more effectively than either AxdAdB-3 (P < 0.0001) or gemcitabine (P < 0.0001) alone. CONCLUSIONS: Intravesical instillation therapy with AxdAdB-3 in combination with gemcitabine can effectively inhibit the orthotopic bladder cancer in nude mouse, and further relevant clinical studies are guaranteed.

Intelligent diagnosis of major depression disease based on multi-layer brain network.

Introduction: Resting-state brain network with physiological and pathological basis has always been the ideal data for intelligent diagnosis of major depression disease (MDD). Brain networks are divided into low-order networks and high-order networks. Most of the studies only use a single-level network to classify while ignoring that the brain works cooperatively with different levels of networks. This study hopes to find out whether varying levels of networks will provide complementary information in the process of intelligent diagnosis and what impact will be made on the final classification results by combining the characteristics of different networks. Methods: Our data are from the REST-meta-MDD project. After the screening, 1,160 subjects from ten sites were included in this study (597 MDD and 563 normal controls). For each subject, we constructed three different levels of networks according to the brain atlas: the traditional low-order network based on Pearson's correlation (low-order functional connectivity, LOFC), the high-order network based on topographical profile similarity (topographical information-based high-order functional connectivity, tHOFC) and the associated network between them (aHOFC). Two sample t-test is used for feature selection, and then features from different sources are fused. Finally, the classifier is trained by a multi-layer perceptron or support vector machine. The performance of the classifier was evaluated using the leave-one-site cross-validation method. Results: The classification ability of LOFC is the highest among the three networks. The classification accuracy of the three networks combined is similar to the LOFC network. These are seven features chosen in all networks. In the aHOFC classification, six features were selected in each round but not seen in other classifications. In the tHOFC classification, five features were selected in each round but were unique. These new features have crucial pathological significance and are essential supplements to LOFC. Conclusion: A high-order network can provide auxiliary information for low-order networks but cannot improve classification accuracy.

Systematical analysis of ferroptosis regulators and identification of GCLM as a tumor promotor and immunological biomarker in bladder cancer.

Bladder cancer (BCa) is a life-threaten disease with an increasing incidence with age, and immunotherapy has become an important treatment for BCa, while the efficiency of the immune system declines with age. It is vital to reveal the mechanisms of tumor immune microenvironment (TIME) and identify novel immunotherapy targets for BCa. Through analyzing the RNA-seq of TCGA-BLCA cohort, we distinguished two ferroptosis-related BCa clusters, and we discovered that in comparation with cluster 2, the cluster 1 BCa patients showed higher PD-L1 expression, more unfavorable overall survival and higher tumor stage and grade. XCELL analyses showed that higher level of Th2 cell and Myeloid dendritic cell were enriched in cluster 1, while NK T cell was enriched in cluster 2, and TIDE analysis revealed that cluster 2 was more sensitive to immunotherapy than cluster 1. GSEA analysis implied that Toll-like signaling pathway and JAK_STAT signaling pathway were significantly enriched in cluster 1. Subsequently, through performing bioinformatic analysis and cell experiments, we demonstrated that GCLM is overexpressed in BCa and indicates dismal prognosis, and knockdown of GCLM can significantly suppress the colony formation ability of BCa cells. Furthermore, we also found that GCLM might be correlated with immune infiltration in BCa, and can serve as a tumor promotor and immunological biomarker in BCa, our research showed the vital roles of ferroptosis regulators in TIME of BCa, and GCLM is a latent therapeutic target for cancer immunotherapy.

Distinguishing between metastatic and benign adrenal masses in patients with extra-adrenal malignancies.

Background and Objectives: The adrenal gland is a common organ involved in metastasis. This study aimed to compare adrenal metastases (AMs) and adrenal benign masses (ABMs) of patients with extra-adrenal malignancies during the staging or follow-up. Methods: We retrospectively collected data from 120 patients with AMs and 87 patients with ABMs. The clinical characteristics, imaging features, pathology, and treatment regimes were analyzed. Results: The most common types of extra-adrenal malignancies in patients with ABMs included thyroid, kidney, and gynecological cancers. On the other hand, lung and kidney cancers and lymphoma were the most frequent primary cancers of AMs. The age and incidence of symptoms were significantly higher in patients with AM. Radiological analysis showed that AMs tended to have larger tumor sizes and higher attenuation values than ABMs on pre-contrast computed tomography (CT). The diagnostic accuracy of positron emission tomography-CT for AM was 94.1%. An adrenal biopsy had a diagnostic accuracy of 92.5%. A multivariate logistic regression model demonstrated that the origins of extra-adrenal malignancies, the enhancement pattern, and attenuation values in pre-contrast CT were independent predictors of AMs. The sensitivity and specificity of this predictive model of combination was 92.5% and 74.1%, respectively. Conclusions: The differential diagnosis between AMs and ABMs is extremely important. The combination of origin of first malignancy, enhancement pattern and CT value in non-enhanced phase is a valuable model for predicting AMs.

Simulating androgen receptor selection in designer yeast.

Androgen receptor (AR) mutation is closely associated with prostate cancer (PCa) and is one of the mechanisms of resistance to PCa therapies such as AR antagonists. Although sequencing technologies like next-generation sequencing (NGS) contributes to the high-throughput and precise detection of AR mutations carried by PCa patients, the lack of interpretations of these clinical genetic variants has still been a roadblock for PCa-targeted precision medicine. Here, we established a designer yeast reporter assay to simulate natural androgen receptor (AR) selection using AR antagonists. Yeast HIS3 gene transactivation was associated with the ligand-induced recruitment of steroid receptor coactivator-1 (SRC-1) by AR mutants, where yeast growth in histidine-free medium was determined as the outcome. This assay is applicable to determine a wide range of clinical AR mutants including those with loss of function relating to androgen insensitivity syndrome (AIS), and those associated with PCa conferring resistance to AR antagonists such as enzalutamide (ENZ), bicalutamide (BIC), and cyproterone acetate (CPA). One clinical AR mutant previously reported to confer ENZ-resistance, F877L, was found to confer partial resistance to CPA as well using designer yeast. Our simple and efficient assay can enable precise one-pot screening of AR mutants, providing a reference for tailored medicine.

[Type V phosphodiesterase inhibitor erection-provoking test with audio-visual sexual stimulation for the diagnosis of erectile dysfunction].

OBJECTIVE: To evaluate the type V phosphodiesterase (PDE-5) inhibitor erection-provoking test with audio-visual sexual stimulation in the diagnosis of erectile dysfunction. METHODS: A total of 853 out-patients diagnosed with erectile dysfunction were divided into an injury and a non-injury group. After scored on IIEF-5 questionnaires, all the patients received oral administration of PDE-5 inhibitors and, 30 minutes later, audio-visual sexual stimulation. The data on penile erection were recorded with Rigiscan Plus. RESULTS: The patients with mild, moderate and severe ED accounted for 18.8, 31.9 and 49.3% in the injury group, and 50.6, 39.8 and 9.6% in the non-injury group, with statistic differences between the two groups in the mild and severe parts (P < 0.05). The rates of conspicuous effectiveness, effectiveness, ineffectiveness and total effectiveness of the combined method were 13.0, 14.5, 72.5 and 27.5% in the injury group, but 55.7, 20.7, 23.6 and 76.4% in the non-injury group, with significant differences (P < 0.05). CONCLUSION: The PDE-5 inhibitor erection-provoking test with audio-visual sexual stimulation is a simple, practical, safe and effective method for the differentiation of organic from psychological erectile dysfunction.

Surgical treatment of a rare case of penile squamous cell carcinoma in a 65-year-old man.

Penile squamous cell carcinoma has been commonly reported in the past decades. We describe a rare case of a huge squamous cell carcinoma of the penis in a 65-year-old patient with a 4-year history of tumor growth, for which total penectomy, perineal urethrostomy and bilateral inguinal lymphadenectomy were carried out. We suggest that aggressive surgical intervention should be recommended for those with well-differentiated penile carcinoma regardless of the size of the tumor.

[Deep sarcoma of the penis: a report of 2 cases and review of the literature].

OBJECTIVE: To investigate the clinical characteristics, diagnosis, treatment and prognosis of deep sarcoma of the penis. METHODS: The pathological and clinical data of 2 cases of deep sarcoma of the penis were analyzed retrospectively and the literature reviewed. RESULTS: Both of the cases were treated by total penectomy. Epithelioid angiosarcoma of the penis was confirmed by postoperative pathology in one patient, who died of pulmonary metastasis in the eighth month after the operation; and epithelioid sarcoma of the penis was confirmed in the other, who died of brain metastasis in the second month after the operation. CONCLUSION: Deep sarcoma of the penis is rare but can be diagnosed pathologically. Total penectomy is the main option for its treatment. Node dissection, with poor prognosis, is not recommended unless adenopathy is palpable.

[Observation of safety and efficacy of tadalafil for men with erectile dysfunction].

OBJECTIVE: To observe the safety and efficacy of tadalafil in the treatment of erectile dysfunction in clinical research. METHODS: Eighty patients with ED, before and after 20 mg tadalafil administered orally, received respectively the rigiscan examination with aural and visual sexual stimulation at the same time, and then Bphallic circumference variation, stiffness index, duration were compared before and after the treatment. RESULTS: Phallic stiffness index, duration revealed a statistically (P < 0.05) obvious improvement before and after the treatment for all patients. A significant difference (P < 0.01) on the phallic stiffness index, duration were found between the patients with psychogenic ED and others with organic or mixed ED after the treatment. Overall satisfaction with tadalafil was 82.5%. There was an obvious difference on the curative rates between the patients with psychogenic ED (92.3%) and others with organic ED (68.7%) or mixed ED (58.3%). All adverse events (11 cases of headache and dizziness, 8 cases of digestive canal unwell, 5 cases of flushing, 2 cases of back muscle pain) associated with tadalafil were mild and recovered without any treatment. CONCLUSION: Tadalafil improves erectile function significantly in most patients. Adverse reactions are generally transient and mild to moderate in nature.

PRDM16 is associated with evasion of apoptosis by prostatic cancer cells according to RNA interference screening.

Histone methylation, which is regulated by histone methyltransferases (HMTs) and histone demethylases (HDMs), has been indicated to be involved in a variety of diseases, particularly in cancer, including androgen­independent prostate cancer (PCa). However, the functions of HMTs and HDTs in cancer have largely remained elusive. The present study, utilized an RNA interference screening using a lentiviral small hairpin (sh)RNA library to systematically elucidate the function of HMTs and HDTs in PCa cell growth and viability. Nine HMTs and HDTs, namely FBXO11, PRDM10, JMJD8, MLL, SETD4, JMJD7, PRMT2, MEN1 and PRDM16, were identified to affect DU145 cell viability, as indicated by an MTS assay subsequent to knockdown of the specific genes using shRNA pools. Furthermore, flow cytometric analysis and western blot analysis of apoptosis­associated proteins indicated that PRDM16 has an anti­apoptotic role in PCa cells. In addition, the spliced form, sPRDM16/MEL1S, was detected to be overexpressed in PCa cell lines. In conclusion, the present study indicated an important oncogenic role of sPRDM16/MEL1S in PCa and suggested that PRDM16 may represent a novel therapeutic target.

Diagnosis and treatment of penile verrucous carcinoma.

Penile verrucous carcinoma is an extremely rare disease that, at present, has not been well characterized. The etiology, diagnosis and treatment of this carcinoma remain poorly understood, particularly in the Chinese population. The aim of the present study was to discuss the methods of diagnosis and treatment of penile verrucous carcinoma in the Chinese population. The clinical and pathological data of 10 patients with penile verrucous carcinoma were analyzed alongside a literature review. All the tumors were exophytic papillary lesions, ranging between 0.4 and 4 cm in diameter and all 10 patients underwent partial penectomy with tumor-negative surgical margins. None of the 10 patients underwent ilioinguinal lymphadenectomy. All patients were regularly followed up for 0.7-9 years, which revealed that no patients developed recurrence, and only one case resulted in mortality due to unassociated causes. It was found that penile verrucous carcinoma is a well-differentiated disease with low malignant potential and locally aggressive features, which seldom metastasizes to regional lymph nodes or distant regions. However, misdiagnosis may occur due to an incorrect biopsy. Favorable outcomes can be achieved by surgery, even without any adjuvant therapy, but patients should be carefully followed up.

Consumption of hydrogen-rich water protects against ferric nitrilotriacetate-induced nephrotoxicity and early tumor promotional events in rats.

The aim of this work was to test whether consumption with hydrogen-rich water (HW) alleviated renal injury and inhibited early tumor promotional events in Ferric nitrilotriacetate (Fe-NTA)-treated rats. Rats were injected with Fe-NTA solution (7.5mg Fe/kg body weight) intraperitoneally to induce renal injury and simultaneously treated with HW (1.3 ± 0.2mg/l). We found that consumption with HW ameliorated Fe-NTA-induced renal injuries including suppressing elevation of serum creatinine and blood urea nitrogen and inhibited early tumor promotional events including decreasing ornithine decarboxylase activity and incorporation of [3H]thymidine into renal DNA. Consumption with HW suppressed Fe-NTA-induced oxidative stress through decreasing formation of lipid peroxidation and peroxynitrite and activities of NADPH oxidase and xanthine oxidase, increasing activity of catalase, and restoring mitochondrial function in kidneys. Consumption with HW suppressed Fe-NTA-induced inflammation marked by reduced NF-κB, IL-6, and MCP-1 expression and macrophage accumulating in kidneys. In addition, consumption with HW suppressed VEGF expression, STAT3 phosphorylation and PCNA expression in kidneys of Fe-NTA-treated rats. Consumption with HW decreased the incidence of renal cell carcinoma and suppressed tumor growth in Fe-NTA-treated in rats. In conclusion, drinking with HW attenuated Fe-NTA-induced renal injury and inhibited early tumor promotional events in rats.