Photodynamic therapy of vaginal intraepithelial neoplasia-How to do it?

Vaginal intraepithelial neoplasia (VaIN or VAIN), a rare precancerous disease, is difficult to treat. Photodynamic therapy (PDT) is a relatively new modality for the treatment of various precancerous mucosal lesions of the lower genital organs, including VaIN. Due to the special structure and location of the vagina, it is difficult to apply photosensitizer and light irradiation to VaIN lesions. This article provides a tutorial guide on the application of ALA-mediated intravaginal PDT for the treatment of VaIN lesions under different situations.

Celastrus orbiculatus extract reverses precancerous lesions of gastric cancer by inhibiting autophagy via regulating the PDCD4-ATG5 signaling pathway.

OBJECTIVES: Celastrus orbiculatus ethyl acetate extract (COE) is the main extract of the stem of the Chinese herbal C. orbiculatus, which has anti-tumor and anti-inflammatory biological effects. Our previous study showed that COE had a certain reversal effect on the precancerous lesions of gastric cancer (PLGC) in rats, but the exact mechanism of action remains elusive. We aimed to explore the therapeutic effects of COE on PLGC and the potential mechanisms. METHODS: The PLGC rat model was successfully constructed by N-methyl-N´-nitro-N-nitrosoguanidine (MNNG) multifactorial induction method. Then, COE was prepared to treat the PLGC rat model. Hematoxylin & eosin staining was used to observe gastric mucosal lesions in rats, AB-PAS and HID-AB staining were used to observe intestinal metaplasia. PDCD4-ATG5 signaling pathway was detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR) in vivo, and autophagy level was detected by IHC, transmission electron microscopy, and RT-PCR in vivo. Besides, the PLGC (MC) cell model was successfully constructed by treating GES-1 cells with MNNG. Then, the morphology, proliferation, and apoptosis of MC cells, and the role of the PDCD4-ATG5 signaling pathway and autophagy in MC cells were evaluated by COE and after the overexpression of PDCD4 treatment. KEY FINDINGS: COE significantly improved gastric mucosal injury and cellular heteromorphism and retarded the progression of PLGC in rats. Further studies indicated COE not only inhibited the level of autophagy but also interfered with the PDCD4-ATG5 signaling pathway in vivo. On the other hand, COE treatment could effectively reverse MC cell damage, inhibit MC cell proliferation, and promote MC cell apoptosis. Furthermore, COE also promoted PDCD4 and inhibited ATG5 expression in vitro, and the inhibitory effect of COE on ATG5-mediated autophagy was further enhanced after the overexpression of PDCD4. CONCLUSIONS: The study revealed that COE could regulate the PDCD4-ATG5 signaling pathway to inhibit autophagy in gastric epithelial cells, which contributes to reversing the progression of PLGC.

(-)-Asarinin alleviates gastric precancerous lesions by promoting mitochondrial ROS accumulation and inhibiting the STAT3 signaling pathway.

BACKGROUND: (-)-Asarinin (Asarinin) is the primary component in the extract of the herb Asarum sieboldii Miq. It possesses various functions, including pain relief, anti-viral and anti-tuberculous bacilli effects, and inhibition of tumor growth. Gastric precancerous lesion (GPL) is a common but potentially carcinogenic chronic gastrointestinal disease, and its progression can lead to gastric dysfunction and cancer development. However, the protective effects of asarinin against GPL and the underlying mechanisms remain unexplored. METHODS: A premalignant cell model (methylnitronitrosoguanidine-induced malignant transformation of human gastric epithelial cell strain, MC cells) and a GPL animal model were established and then were treated with asarinin. The cytotoxic effect of asarinin was assessed using a CCK8 assay. Detection of intracellular reactive oxygen species (ROS) using DCFH-DA. Apoptosis in MC cells was evaluated using an annexin V-FITC/PI assay. We performed western blot analysis and immunohistochemistry (IHC) to analyze relevant markers, investigating the in vitro and in vivo therapeutic effects of asarinin on GPL and its intrinsic mechanisms. RESULTS: Our findings showed that asarinin inhibited MC cell proliferation, enhanced intracellular ROS levels, and induced cell apoptosis. Further investigations revealed that the pharmacological effects of asarinin on MC cells were blocked by the ROS scavenger N-acetylcysteine. IHC revealed a significant upregulation of phospho-signal transducer and activator of transcription 3 (p-STAT3) protein expression in human GPL tissues. In vitro, asarinin exerted its pro-apoptotic effects in MC cells by modulating the STAT3 signaling pathway. Agonists of STAT3 were able to abolish the effects of asarinin on MC cells. In vivo, asarinin induced ROS accumulation and inhibited the STAT3 pathway in gastric mucosa of mice, thereby halting and even reversing the development of GPL. CONCLUSION: Asarinin induces apoptosis and delays the progression of GPL by promoting mitochondrial ROS production, decreasing mitochondrial membrane potential (MMP), and inhibiting the STAT3 pathway.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

The Anticancer Effects of the Garlic Organosulfide Diallyl Trisulfide through the Attenuation of B[a]P-Induced Oxidative Stress, AhR Expression, and DNA Damage in Human Premalignant Breast Epithelial (MCF-10AT1) Cells.

Benzo[a]pyrene (B[a]P) is the most characterized polycyclic aromatic hydrocarbon associated with breast cancer. Our lab previously reported that the organosulfur compound (OSC), diallyl trisulfide (DATS), chemoprevention mechanism works through the induction of cell cycle arrest and a reduction in oxidative stress and DNA damage in normal breast epithelial cells. We hypothesize that DATS will inhibit B[a]P-induced cancer initiation in premalignant breast epithelial (MCF-10AT1) cells. In this study, we evaluated the ability of DATS to attenuate B[a]P-induced neoplastic transformation in MCF-10AT1 cells by measuring biological endpoints such as proliferation, clonogenicity, reactive oxygen species (ROS) formation, and 8-hydroxy-2-deoxyguanosine (8-OHdG) DNA damage levels, as well as DNA repair and antioxidant proteins. The results indicate that B[a]P induced proliferation, clonogenic formation, ROS formation, and 8-OHdG levels, as well as increasing AhR, ARNT/HIF-1ß, and CYP1A1 protein expression compared with the control in MCF-10AT1 cells. B[a]P/DATS's co-treatment (CoTx) inhibited cell proliferation, clonogenic formation, ROS formation, AhR protein expression, and 8-OHdG levels compared with B[a]P alone and attenuated all the above-mentioned B[a]P-induced changes in protein expression, causing a chemopreventive effect. This study demonstrates, for the first time, that DATS prevents premalignant breast cells from undergoing B[a]P-induced neoplastic transformation, thus providing more evidence for its chemopreventive effects in breast cancer.

Evaluation of the effectiveness and safety of photodynamic therapy in the treatment of precancerous diseases of the cervix (neoplasia) associated with the human papillomavirus: A systematic review.

This study provides an overview of the effectiveness and safety of PDT for the treatment of HPV-associated precancerous cervical conditions and contains recent findings from relevant research studies. A comprehensive literature search of MEDLINE/PubMed, Cochrane Central Library, and Google Scholar was conducted, including analytic epidemiological studies, and 11 papers were included. The narrative synthesis approach was used to summarize the results of the included studies. Studies were critically appraised using The Joanna Briggs Institute (JBI) tool for assessing the risk of bias. The results of the study demonstrate that CRR for HPV remission ranges from 66.7 % to 92.73 %, whereas for CIN1 it fluctuates from 57.1 % to 83.3 %. The frequency of recurrence of the disease ranged from 3.3 % to 8.9 % during the follow-up period of up to 2 years. Adverse events were observed in 8 (66 %) studies and the most common were cervical stenosis, abdominal pain, vaginal pain, and focal edema. Five types of topical and intravenous applications along with lasers of various wavelengths and intensities were mostly used. However, all studies demonstrated relatively similar results. According to the results, PDT has demonstrated favorable outcomes, but no impressive effect on the treatment of CIN. It should be emphasized, that the effectiveness of PDT for the treatment of HPV-associated CIN may vary depending on some variables, including the kind of PDT agent used, the dosage, duration and frequency of PDT administration, the severity and location of the lesions, and the host immunological response.

The combination of holmium laser and ALA-PDT for Bowenoid Papulosis with diffuse large B-cell lymphoma.

Bowenoid Papulosis (BP) is an anogenital pre-malignancy. BP with immunosuppression may recur, worsen, or possibly evolve into squamous cell carcinoma or Bowen's disease (BD), and it may also become resistant to conventional treatment. Here, we describe a complex case of BP together with BD and Diffuse Large B-Cell Lymphoma that was effectively treated with a holmium laser in conjunction with 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT). The lesion totally vanished and the affected area remained intact with no recurrence at five years.

Quality evaluation of the literature on clinical randomized controlled trials of traditional Chinese medicine for treatment of gastric precancerous lesions in the past 20 years. / ä¸­åŒ»è¯æ²»ç–—èƒƒç™Œå‰ç— å˜ä¸´åºŠéšæœºå¯¹ç §è¯•éªŒäºŒåå¹´æ–‡çŒ®è´¨é‡è¯„ä»·.

OBJECTIVES: To evaluate the methodological quality of randomized controlled trials (RCTs) of traditional Chinese medicines for the treatment of gastric precancerous lesions in the past 20 years. METHODS: The RCTs on traditional Chinese medicines for gastric precancerous lesions were searched from the CNKI, Wanfang database, VIP, PubMed, and Embase from January 2001 to December 2021. The retrieved articles were screened, extracted and evaluated based on the 2010 edition of CONSORT statement, Cochrane Risk of Bias Assessment Scale and additional evaluation indicators. RESULTS: A total of 840 papers were included. According to the Cochrane Risk of Bias Assessment Scale, the high risk of bias in the application of randomized methods was 5.95%; the risk of uncertainty for the allocation scheme concealment was 98.93%; the risk of uncertainty for blinding of patients or testers was 98.69%; the risk of uncertainty for blinding of the outcome assessor was 100.00%; the risk of bias for completeness of the outcome data was 2.86%; and the risk of uncertainty for selective reporting was 98.45%. The CONSORT statement evaluating the quality of reporting showed that 100.00% of the RCT articles reported the 8 entries; 36.79% of the literature mentioned the method of randomized sequence generation, but only 27.62% of the literature mentioned who implemented the randomized program, 1.07% of the literature hid the randomized program and 1.31% of the studies were blinded; 36.67% of the literature reported adverse reactions; no literature reported sample size prediction methods. Additional evaluation indicators showed that 17.02% of the studies had ethical approval; 43.81% of the literature specified Chinese medicine evidence; 16.55% of the studies excluded severe heterotrophic hyperplasia; 7.26% of the studies conducted follow-up; and 65.12% of the literature used composite efficacy indicators; 46.67% of the literature applied pathological histological evaluation; 2.62% of the literature applied quality of life evaluation. CONCLUSIONS: The overall risk of bias in RCTs of traditional Chinese medicines for gastric precancerous lesions is high, and the quality of most of the study reports needs to be improved. In the future, it is necessary to strengthen the study design of RCTs and refer to appropriate traditional Chinese medicines evidence grading standards, select study protocols according to different purposes, provide objective and strong evidence for clinical studies on traditional Chinese medicines, and carry out clinical study design and result reporting suitable for traditional Chinese medicines according to the CONSORT principle.

Novel tetrahydrocurcumin integrated mucoadhesive nanocomposite κ-carrageenan/xanthan gum sponges: a strategy for effective local treatment of oral cancerous and precancerous lesions.

Oral cancer is one of the leading causes of death worldwide. Oral precancerous lesions (OPL) are the precursors of oral cancer, with varying degrees of progression. Tetrahydrocurcumin (THC) is a major metabolite of curcumin with superior anticancer properties against various types of cancer. However, THC's clinical outcome is limited by its poor aqueous solubility. Herein, we developed novel mucoadhesive biopolymer-based composite sponges for buccal delivery of THC, exploiting nanotechnology and mucoadhesion for efficient prevention and treatment of oral cancer. Firstly, THC-nanocrystals (THC-NC) were formulated and characterized for subsequent loading into mucoadhesive composite sponges. The anticancer activity of THC-NC was assessed on a human tongue squamous carcinoma cell line (SCC-4). Finally, the chemopreventive activity of THC-NC loaded sponges (THC-NC-S) was examined in DMBA-induced hamster OPL. The selected THC-NC exhibited a particle size of 532.68 ± 13.20 nm and a zeta potential of -46.08 ± 1.12 mV. Moreover, THC-NC enhanced the anticancer effect against SCC-4 with an IC50 value of 80 µg/mL. THC-NC-S exhibited good mucoadhesion properties (0.24 ± 0.02 N) with sustained drug release, where 90% of THC was released over 4 days. Furthermore, THC-NC-S had a magnificent potential for maintaining high chemopreventive activity, as demonstrated by significant regression in the dysplasia degree and a decline in cyclin D1 (control: 40.4 ± 12.5, THC-NC-S: 12.07 ± 5.2), culminating in significant amelioration after 25 days of treatment. Conclusively, novel THC-NC-S represent a promising platform for local therapy of OPL, preventing their malignant transformation into cancer.

Imiquimod as Local Immunotherapy in the Management of Premalignant Cutaneous Conditions and Skin Cancer.

Cutaneous cancers are, by far, the most common malignant neoplasms of the human being. Due to the great array of clinical conditions, their worldwide increasing incidence and the steady ageing of the population, non-invasive treatments modalities that show a good clinical response, a proper benefit-risk ratio and cosmetic results are becoming increasingly important in the clinical setting. Imiquimod is a topically applied immunomodulator which is often used in the management of several premalignant and malignant cutaneous disorders. This article is a review of the current literature on its mechanism of action, pharmacokinetics, and therapeutical effects.

Skin-Limited, Methotrexate-Associated Epstein-Barr Virus-Positive Mucocutaneous Ulcer-A Mimicker of High-Grade Lymphoma. A Report of 4 Cases and Review of the Literature.

ABSTRACT: Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) constitute a diverse range of conditions including posttransplant lymphoproliferative disorders, other iatrogenic IA-LPDs, and lymphoproliferative disorders associated with an underlying primary immune disorder or HIV infection. IA-LPDs are clinically and pathologically heterogeneous, and there is a lack of standardization of diagnostic terminology. They can represent a potential serious diagnostic pitfall because the histological features of clinically indolent proliferations may mimic those of high-grade lymphoma. However, correct identification of these entities is essential given that complete remission may occur upon reversal of the underlying cause of immunosuppression without the need for systemic therapy. IA-LPDs presenting in the skin are rare but well documented. One form of iatrogenic IA-LPD, methotrexate-associated lymphoproliferative disorder (MTX-LPD), can present with cutaneous nodules, plaques, or ulcers. Predominantly, MTX-LPD develops in the context of long-term treatment of autoimmune conditions, such as rheumatoid arthritis, dermatomyositis, and Sjögren syndrome, and may be associated with underlying Epstein-Barr virus (EBV) infection. We present 4 cases of cutaneous EBV-positive B-cell MTX-LPD and describe their clinical and morphological findings. Comparison of our histological findings to the diagnostic criteria for EBV-positive mucocutaneous ulcer (EBVMCU) revealed significant overlap, highlighting the intersection between MTX-LPD and EBVMCU. Withdrawal of methotrexate resulted in healing of all lesions at a mean time of 2 months. In summary, close clinicopathological correlation is vital to identify MTX-LPD presenting as cutaneous EBVMCU given that the initial treatment strategy is that of withdrawal of methotrexate without the need for immediate systemic therapy.

Therapeutic Effects of Huazhuojiedu Decoction on Precancerous Lesions of Gastric Cancer by Regulating Mitophagy.

This research aims to explore the therapeutic effect and potential mechanisms of Huazhuojiedu decoction (HZJD) for alleviating precancerous lesions of gastric cancer (PLGC) both in vivo and in vitro. HZJD is a traditional Chinese herbal formula consisting of 11 herbs. Sprague-Dawley (SD) rats were randomly divided into four subgroups: control group, model group, positive drug group, and HZJD group. Hematoxylin-eosin (H&E) staining, high iron diamine-alcian blue (HID-AB) staining, alcian blue-periodic acid Schiff (AB-PAS) staining, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blot assays were performed after 10 weeks of HZJD treatment. In vitro, the cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. RT-qPCR and Western blot assays were performed to evaluate mitophagy levels. The results indicated that HZJD could retard the pathological progression in PLGC rats and reduce PLGC cell proliferation. Treatment with HZJD significantly increased the mRNA and protein expression levels of Sirt3, Foxo3a, Parkin, and LC3 II/I, while decreasing the mRNA and protein expression levels of p62 and Tomm20. HZJD was found to have the ability to reverse the decline in mitophagy activity both in vivo and in vitro. In conclusion, the study assessed the impact of HZJD and provided evidence regarding its potential molecular mechanism.

Elian granules alleviate precancerous lesions of gastric cancer in rats by suppressing M2-type polarization of tumor-associated macrophages through NF-κB signaling pathway.

BACKGROUND: Precancerous lesions of gastric cancer (PLGC) refer to a kind of histopathological changes in the gastric mucosa that can progress to gastric cancer. Elian granules (ELG), a Chinese medicinal prescription, have achieved satisfactory results in the treatment of PLGC. However, the exact mechanism underlying the therapeutic effect of ELG remains unclear. Here, this study aims to explore the mechanism of ELG alleviating PLGC in rats. METHODS: The chemical ingredients of ELG were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Specific Pathogen Free SD rats were randomly assigned to 3 groups: the control, model, and ELG groups. The 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) integrated modeling method was adopted to construct the PLGC rat model in groups except for the control group. Meanwhile, normal saline was used as an intervention for the control and model groups, and ELG aqueous solution for the ELG group, lasting 40 weeks. Subsequently, the stomach of rats was harvested for further analysis. Hematoxylin-eosin staining of the gastric tissue was conducted to assess the pathological changes. Immunofluorescence was carried out for the expression of CD68, and CD206 proteins. Real-time quantitative PCR combined with Western blot was conducted to analyze the expression of arginase-1(Arg-1), inducible nitric oxide synthase (iNOS), p65, p-p65, nuclear factor inhibitor protein-α (IκBα), and p-IκBα in gastric antrum tissue. RESULTS: Five chemical ingredients including Curcumol, Curzerenone, Berberine, Ferulic Acid, and 2-Hydroxy-3-Methylanthraquine were identified in ELG. The gastric mucosal glands of rats treated with ELG were orderly arranged, with no intestinal metaplasia and no dysplasia. Furthermore, ELG decreased the percentage of M2-type TAMs marked with CD68 and CD206 proteins, and the ratio of Arg-1 to iNOS in the gastric antrum tissue of rats with PLGC. In addition, ELG could also down-regulate the protein and mRNA expression of p-p65, p65, and p-IκBα, but up-regulate the expression of IκBα mRNA in rats with PLGC. CONCLUSIONS: The results showed that ELG attenuates PLGC in rats by suppressing the M2-type polarization of tumor-associated macrophages (TAMs) through NF-κB signaling pathway.

Effect of Busulfan and Treosulfan on Gonadal Function after Allogeneic Stem Cell Transplantation in Children and Adolescents with Nonmalignant Diseases Is Not Exposure-Dependent.

With an increasing number of young patients surviving into adulthood after hematopoietic stem cell transplantation (HSCT), gonadal dysfunction becomes an important late effect with significant impact on quality of life. In this retrospective study, we evaluated the exposure of busulfan (Bu) and treosulfan (Treo) in relation to gonadal function in pediatric patients who underwent HSCT for a nonmalignant disease between 1997 and 2018. In the Bu group, 56 patients could be evaluated, and gonadal dysfunction was found in 35 (63%). Lower Bu exposure (ie, cumulative area under the curve [AUC] <70 mg*h/L) was not associated with a reduced risk of gonadal dysfunction (odds ratio [OR], .92; 95% confidence interval [CI], .25 to 3.49; P = .90). In the Treo cohort, 32 patients were evaluable and gonadal insufficiency occurred in 9 patients (28%). Lower Treo exposure (AUC <1750 mg*h/L on day 1) was not associated with a reduced risk of gonadal dysfunction (OR, 1.6; 95% CI, .16 to 36.6; P = .71). Our data do not support the premise that reduced-intensity Bu-based conditioning reduces the risk for gonadal toxicity, and it is unlikely that therapeutic drug monitoring-based reduced treosulfan exposure will further limit the risk of gonadal dysfunction.

Effects of vitamin D supplementation on inflammatory response in patients with cancer and precancerous lesions: Systematic review and meta-analysis of randomized trials.

BACKGROUND & AIMS: Inflammation plays a key role in tumor development and progression. Vitamin D has potential tumor suppressing effects through modulation of inflammatory processes. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to summarize and evaluate the effects of vitamin D3 supplementation (VID3S) on serum inflammatory biomarkers among patients with cancer or pre-cancerous lesions. METHODS: We searched PubMed, Web of Science and Cochrane databases until November 2022. The effects of VID3S were estimated from pooled standardized mean differences (SMDs) with their 95% confidence intervals (CIs) for inflammatory biomarker follow-up levels between intervention and control groups. RESULTS: Meta-analysis of eight RCTs (total of 592 patients with cancer or pre-cancerous conditions) showed that VID3S significantly lowered levels of serum tumor necrosis factor (TNF)-α (SMD [95%CI]: -1.65 [-3.07; -0.24]). VID3S also resulted in statistically non-significantly lower serum levels of interleukin (IL)-6 (SMD [95%CI]: -0.83, [-1.78; 0.13]) and C-reactive protein (CRP) (SMD [95%CI]: -0.09, [-0.35; 0.16]), whereas IL-10 levels were unaltered (SMD [95%CI]: -0.00, [-0.50; 0.49]). CONCLUSION: Our study shows evidence of a significant reduction of TNF-α levels by VID3S for patients with cancer or precancerous lesions. Patients with cancer or precancerous lesions may benefit from personalized VID3S in suppressing tumour-promoting inflammatory response. PROSPERO REGISTRATION NUMBER: CRD42022295694.

Er: YAG laser assisted photodynamic therapy for the management of severe oral epithelial dysplasia with innate and adaptive immune responses.

Oral epithelial dysplasia (OED) in oral potentially malignant disorders (OPMDs) increases the risk of malignant transformation. However, the management of OED is not well defined. Photodynamic therapy (PDT) is a hypotoxic, highly selective and minimally-invasive operation which reduces morbidity and disfigurement greatly. Additionally, laser ablation guaranteed a better penetration for topical application of 5-aminolaevulinic acid (ALA)-PDT. Herein, we present a case of a large lesion of oral leukoplakia (OLK) in left tongue dorsum and lateral margin, pathologically manifested as severe epithelial dysplasia (SED). We firstly discussed the feasibility of Er: YAG laser assisted PDT for the treatment of SED in OPMDs. The patient achieved complete remission at 1 year follow-up. Downregulated number of p53 and Ki67 positive cells were observed in the tissues after Er: YAG laser assisted PDT. In addition, increased CD8+ positive cells infiltrated around the tissues and increased natural killer (NK) cells level were detected in the peripheral blood. In summary, Erbium:yttrium-aluminum-garnet (Er:YAG) laser assisted PDT is an effective and promising treatment for the management of SED in OPMDs with innate and adaptive immune responses.

Developmental synergism in the management of oral potentially malignant disorders.

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the oral cavity or lips. The unifying theme of OPMDs is their potential risk for cancer development. Therefore, the primary objective of the management should be to prevent carcinogenesis. Beyond diagnosis, current strategies for the management of OPMDs predominantly include non-surgical and surgical interventions and a "watch-and-see" approach, such as disease monitoring or surveillance, and preventive strategies. Though no optimal clinical treatment has gained universal approval for reducing or preventing malignant development of OPMDs. Therefore, an urgent need exits for improved treatment properties and effective predictive markers for OPMDs treatment. This review aims to outline recent synergism regarding to the management of OPMDs. Developing new technologies and improved application parameters to promote the treatment efficacy and a novel management prescription approach to OPMDs are proposed.

Worth a Pound of Cure? Emerging Strategies and Challenges in Cancer Immunoprevention.

Cancer immunoprevention applies immunologic approaches such as vaccines to prevent, rather than to treat or cure, cancer. Despite limited success in the treatment of advanced disease, the development of cancer vaccines to intercept premalignant states is a promising area of current research. These efforts are supported by the rationale that vaccination in the premalignant setting is less susceptible to mechanisms of immune evasion compared with established cancer. Prophylactic vaccines have already been developed for a minority of cancers mediated by oncogenic viruses (e.g., hepatitis B and human papillomavirus). Extending the use of preventive vaccines to non-virally driven malignancies remains an unmet need to address the rising global burden of cancer. This review provides a broad overview of clinical trials in cancer immunoprevention with an emphasis on emerging vaccine targets and delivery platforms, translational challenges, and future directions.

Vulvar intraepithelial neoplasia, grade III, treated with photodynamic therapy: A case report.

Vulvar intraepithelial neoplasia (VIN) is a precancerous lesion on the vulvar epidermis that does not invade or metastasize to surrounding stroma; it manifests as atypical intraepithelial hyperplasia on the vulva. Most patients with VIN are diagnosed early, and treatment with standardized therapy often leads to complete regression of symptoms. The treatment of VIN is still a challenge for clinicians because, in most cases, surgery is destructive and risky. However, photodynamic therapy (PDT) was recommended as a new treatment for VIN. Herein, we report the case of a patient with a large-area high-grade VIN lesion complicated by human papillomavirus infection. The patient could not undergo surgical treatment. However, treatment with PDT was performed in our outpatient department. There was slight pain during the treatment after multi-point injection of micro-lidocaine (0.05 mL/dot) was given. No recurrence was noted after 13 months of follow-up. More importantly, scarring and other major side effects were not detected. Therefore, PDT can be a useful alternative treatment for patients with VIN with large lesions or multifocal high-grade VIN.