A low molecular weight multifunctional theranostic molecule for the treatment of prostate cancer.

Rationale: Although surgery and radiation therapy in patients with low risk prostate cancer appear appropriate and effective, those with high-risk localized disease almost always become hormone refractory and then rapidly progress. A new treatment strategy is urgently needed for patients with high-risk localized prostate cancer, particularly an approach that combines two drugs with different mechanisms. Combinations of photodynamic therapy (PDT) and chemotherapy have shown synergistic effects in clinical trials, but are limited by off-target toxicity. Prostate specific membrane antigen (PSMA) is a well-established biomarker for prostate cancer. Here we describe the use of a PSMA ligand to selectively and simultaneously deliver a potent microtubule inhibiting agent, monomethyl auristatin E (MMAE), and a PDT agent, IR700, to prostate cancers. Methods: Using a bifunctional PSMA ligand PSMA-1-Cys-C6-Lys, we created a novel theranostic molecule PSMA-1-MMAE-IR700. The molecule was tested in vitro and in vivo for selectivity and antitumor activity studies. Results: PSMA-1-MMAE-IR700 showed selective and specific uptake in PSMA-positive PC3pip cells, but not in PSMA-negative PC3flu cells both in vitro and in vivo. In in vitro cytotoxicity studies, when exposed to 690 nm light, PSMA-1-MMAE-IR700 demonstrated a synergistic effect leading to greater cytotoxicity for PC3pip cells when compared to PSMA-1-IR700 with light irradiation or PSMA-1-MMAE-IR700 without light irradiation. In vivo antitumor activity studies further showed that PSMA-1-MMAE-IR700 with light irradiation significantly inhibited PC3pip tumor growth and prolonged survival time as compared to mice receiving an equimolar amount of PSMA-1-IR700 with light irradiation or PSMA-1-IR700-MMAE without light irradiation. Conclusion: We have synthesized a new multifunctional theranostic molecule that combines imaging, chemotherapy, and PDT for therapy against PSMA-expressing cancer tissues. This work may provide a new treatment option for advanced prostate cancer.

The Impact of COVID-19 on Dentistry in Yichang, China, and Protective Suggestions for Normalisation of Epidemic Prevention.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been identified as a pandemic by the World Health Organization in March 2020, and it affects all aspects of life, including dental care. OBJECTIVES: The purpose of this article is to explore the impact of COVID-19 on the daily operations of the stomatology department and provide some guidance for dental health care personnel around the world in continuing to provide exemplary care while limiting the spread of COVID-19. MATERIALS AND METHODS: Retrospective analyses were performed on dental patients' medical records from the stomatology department of the First People's Hospital of Yichang, China, which were collected in the pre-epidemic, epidemic, and post-epidemic periods. Hospital-wide triage and stomatology department-specific protocols were established in the hospital to prevent cross-infection during the COVID-19 pandemic. RESULTS: The number of patients decreased and proportion of emergency cases increased during the epidemic period. With prevention protocols in place, the number of dental patients returned to the normal range with a slight elevation during the post-epidemic period. Thus far, there has not been a single documented case of COVID-19 related to dental treatment in the hospital. CONCLUSIONS: COVID-19 has a major impact on daily life, including dental care services. Effective prevention and control measures including 3 levels of protection-zoning, instrumentation, and environmental disinfection-are needed for dental settings to provide care.

Small Molecule-Based Prodrug Targeting Prostate Specific Membrane Antigen for the Treatment of Prostate Cancer.

Metastatic castration-resistant prostate cancer poses a serious clinical problem with poor outcomes and remains a deadly disease. New targeted treatment options are urgently needed. PSMA is highly expressed in prostate cancer and has been an attractive biomarker for the treatment of prostate cancer. In this study, we explored the feasibility of targeted delivery of an antimitotic drug, monomethyl auristatin E (MMAE), to tumor tissue using a small-molecule based PSMA lig-and. With the aid of Cy5.5, we found that a cleavable linker is vital for the antitumor activity of the ligand-drug conjugate and have developed a new PSMA-targeting prodrug, PSMA-1-VcMMAE. In in vitro studies, PSMA-1-VcMMAE was 48-fold more potent in killing PSMA-positive PC3pip cells than killing PSMA-negative PC3flu cells. In in vivo studies, PSMA-1-VcMMAE significantly inhibited tumor growth leading to prolonged animal survival in different animal models, including metastatic prostate cancer models. Compared to anti-PSMA antibody-MMAE conjugate (PSMA-ADC) and MMAE, PSMA-1-VcMMAE had over a 10-fold improved maximum tolerated dose, resulting in improved therapeutic index. The small molecule-drug conjugates reported here can be easily synthesized and are more cost efficient than anti-body-drug conjugates. The therapeutic profile of the PSMA-1-VcMMAE encourages further clin-ical development for the treatment of advanced prostate cancer.

Analysis of anxiety-related factors amongst frontline dental staff during the COVID-19 pandemic in Yichang, China.

BACKGROUND: Dental staff were characterized with the tolerance of enduring stress and they are at a high risk to respiratory infectious disease. This study compared the anxiety level of the frontline dental staff (FDS) to the general public in Yichang during the coronavirus disease of 2019 (COVID-19) pandemic and examined potential explanatory factors to the differences. METHODS: Two online questionnaires were used separately to collect data from FDS and the general public. The Chinese version of Beck Anxiety Inventory (BAI) was included for the assessment of anxiety. Firstly, a Chi-square test was conducted to compare the anxiety state between these two groups. Then, a bivariate analysis using Cramer's V and Eta squared was conducted to find the potential factors. Lastly, a binary logistic regression was performed to examine the association between potential factors and the anxiety state of FDS. RESULTS: In general, FDS were 4.342 (95% CI: 2.427-7.768) times more likely to suffer from anxiety disorders than the general public. The bivariate analysis showed that age, Level Three Protective Measures (PM-3), conflicts with patients and/or colleagues were moderately associated with the anxiety state of FDS. But the knowledge of COVID-19, the treatment to suspected or confirmed cases both had a weak association with the anxiety among FDS. Conversely, workload, the exposure to potential infectious substance and conducting aerosol generated performance were not significantly related to the anxiety of FDS. As the model indicated, an elder age and PM-3 protective measures could lower the anxiety state of FDS, whereas the conflict with patients or/and colleagues would worsen it. CONCLUSIONS: During the COVID-19 pandemic, FDS were more likely to suffer from anxiety disorders than the general public. An elder age, sufficient personal protective measures and good relationships with colleagues and patients would help them to maintain good mental health.

Photodynamic Therapy Is an Effective Adjuvant Therapy for Image-Guided Surgery in Prostate Cancer.

Local and metastatic relapses of prostate cancer often occur following attempted curative resection of the primary tumor, and up to 66% of local recurrences are associated with positive margins. Therefore, technologies that can improve the visualization of tumor margins and adjuvant therapies to ablate remaining tumor tissues are needed during surgical resection of prostate adenocarcinoma. Photodynamic agents have the potential to combine both fluorescence for image-guided surgery (IGS) and photodynamic therapy (PDT) to resect and ablate cancer cells. The objective of this study was to determine the utility of a targeted PDT agent for IGS and adjuvant PDT. Using a previously developed prostate-specific membrane antigen (PSMA)-targeted PDT agent, PSMA-1-Pc413, we showed that PSMA-1-Pc413 selectively highlighted PSMA-expressing tumors, allowing IGS and more complete tumor resection compared with white light surgery. Subsequent PDT further reduced tumor recurrence and extended animal survival significantly. This approach also enabled identification of tumor cells in lymph nodes. In summary, this study presents a potential new treatment option for patients with prostate cancer undergoing surgery, which improves tumor visualization and discrimination during surgery, including identification of cancer in lymph nodes. SIGNIFICANCE: These findings present a photodynamic agent that can be used for both photodynamic therapy and image-guided surgery, allowing better visualization of tumor margins and elimination of residual tumor tissues.