Search Results (24)

Background and Objectives: Human papillomavirus (HPV) is one of the most prevalent sexually transmitted illnesses. HPV is responsible for genital condyloma lesions. A durable and effective systemic treatment regimen has not been established for HPV-related infections. In the present study, our purpose was to evaluate the role of active hexose correlated compound (AHCC) in preventing relapse in patients who underwent cauterization for condyloma accuminata. Materials and Methods: A total of 244 individuals admitted to our hospital between January 2019 and June 2022 were diagnosed as having condyloma acuminata, and those who underwent condyloma cauterization were evaluated retrospectively. We included 133 individuals who met the criteria. Patients who received AHCC were scheduled for follow-up examinations at regular intervals every three months. Patients were divided into two groups and analyzed based on whether they did or did not use AHCC. Results: The average age of AHCC non-users was significantly greater than that of AHCC users (p < 0.01). The number of condylomas and the maximum condyloma diameter of AHCC users before treatment were found to be significantly higher than in AHCC non-users (p = 0.006 and p = 0.004, respectively). Among participants with recurrence, the number and diameter of condylomas in AHCC users were significantly lower than in AHCC non-users (p = 0.019 and p = 0.042, respectively). Conclusions: Although the usage of AHCC is not expected to help prevent recurrence after the cauterization of condylomata acuminate in all patients, physicians may consider AHCC as a nutritional supplement and supportive therapy in the absence of other systemic treatments. Consequently, the duration of AHCC support necessary to optimize the effect of AHCC use on relapse prevention requires further evaluation on the basis of both target IFN-β levels and HPV infection status. Full article

In canine leishmaniosis (CanL), complex interactions between the parasites and the immunological background of the host influence the clinical presentation and evolution of infection and disease. Therefore, the potential use of nutraceuticals as immunomodulatory agents becomes of considerable interest. Some biological principles, mainly derived from plants and referred to as plant-derived nutraceuticals, are considered as supplementation for Leishmania spp. infection. This study provides a systematic review regarding the use of nutraceuticals as a treatment using a text mining (TM) and topic analysis (TA) approach to identify dominant topics of nutritional supplements in leishmaniosis-based research, summarize the temporal trend in topics, interpret the evolution within the last century and highlight any possible research gaps. Scopus^® database was screened to select 18 records. Findings revealed an increasing trend in research records since 1994. TM identified terms with the highest weighted frequency and TA highlighted the main research areas, namely “Nutraceutical supports and their anti-inflammatory/antioxidant properties”, “AHCC and nucleotides in CanL”, “Vit. D3 and Leishmaniosis”, “Functional food effects and Leishmaniosis” and “Extract effects and Leishmaniosis”. Despite the existing academic interest, there are only a few studies on this issue so far, which reveals a gap in the literature that should be filled. Full article

The therapeutic landscape for aHCC has evolved in recent years, necessitating a comprehensive analysis of treatment patterns, clinical outcomes, HCRU, and costs to contextualize emerging treatments. This study aimed to investigate these outcomes using real-world data from Ontario, Canada. This retrospective cohort study was conducted using linked administrative databases from April 2010 to March 2020. Patients diagnosed with aHCC were included, and their clinical and demographic characteristics were analyzed, as well as treatment patterns, survival, HCRU, and economic burden. Among 7322 identified patients, 802 aHCC patients met the eligibility criteria for inclusion in the study. Treatment subgroups included 1L systemic therapy (53.2%), other systemic treatments (4.5%), LRT (9.0%), and no treatment (33.3%). The median age was 66 years, and the majority were male (82%). The mOS for the entire cohort from diagnosis was 6.5 months. However, patients who received 1L systemic therapy had an mOS of 9.0 months, which was significantly higher than the other three subgroups. The mean cost per aHCC-treated patient was $49,640 CAD, with oral medications and inpatient hospitalizations as the largest cost drivers. The results underscore the need for the continuous evaluation and optimization of HCC management strategies in the era of evolving therapeutic options. Full article

A standardized extract of cultured Lentinula edodes mycelia (ECLM, AHCC^®) has been shown to have beneficial effects on organ metabolism. ECLM has been indicated to have liver protective properties by suppressing inflammatory responses. The pathogenesis of hepatic ischemia-reperfusion injury is thought to involve the induction of inflammatory mediators. However, whether ECLM affects inflammatory mediators caused by warm hepatic ischemia-reperfusion injury and partial hepatectomy (HIRI+PH) has not been clarified. In this study, we evaluated the protective effects of ECLM against liver damage caused by HIRI+PH. Rats were fed a normal diet (HIRI+PH) or a normal diet with 2% ECLM (HIRI+PH and ECLM) for ten days, then the liver and duodenal ligament were clamped and subjected to 15 min of hepatic ischemia. After 70% hepatectomy, the inflow occlusion was released, and liver and blood samples were collected at 3, 6, and 24 h. The effect of ECLM on mortality induced by 30 min of ischemia and hepatectomy was evaluated. The results showed that ECLM attenuated pathological liver damage, including apoptosis, in the rats treated with HIRI+PH, and decreased serum aminotransferase activity; ECLM decreased mRNA levels of the inflammation-related genes inducible nitric oxide synthase and C-X-C motif chemokine ligand 1, and increased mRNA levels of interleukin 10, an anti-inflammatory cytokine; ECLM increased hepatocyte growth factor mRNA levels and Ki-67 labeled nuclei in the liver at 24 h; ECLM significantly reduced HIRI+PH-induced mortality. In conclusion, ECLM may prevent HIRI+PH-induced liver injury in part by suppressing various inflammatory responses and promoting liver regeneration. Full article

Chronic lymphocytic leukemia (CLL) is a disease characterized by the accumulation of mature CD19⁺CD5⁺CD23⁺ B cells in the bloodstream and in lymphoid organs. It usually affects people over 70 years of age, which limits the options for treatments. The disease is typically well-managed, but to date is still incurable. Hence, the need for novel therapeutic strategies remains. Nurse-like cells (NLCs) are major components of the microenvironment for CLL, supporting tumor cell survival, proliferation, and even drug resistance. They are of myeloid lineage, guided toward differentiating into their tumor-supportive role by the CLL cells themselves. As such, they are analogous to tumor-associated macrophages and represent a major therapeutic target. Previously, it was found that a mushroom extract, Active Hexose-Correlated Compound (AHCC), promoted the death of acute myeloid leukemia cells while preserving normal monocytes. Given these findings, it was asked whether AHCC might have a similar effect on the abnormally differentiated myeloid-lineage NLCs in CLL. CLL-patient PBMCs were treated with AHCC, and it was found that AHCC treatment showed a direct toxic effect against isolated CLL cells. In addition, it significantly reduced the number of tumor-supportive NLCs and altered their phenotype. The effects of AHCC were then tested in the Eµ-TCL1 mouse model of CLL and the Mll^PTD/WT Flt3^ITD/WT model of AML. Results showed that AHCC not only reduced tumor load and increased survival in the CLL and AML models, but it also enhanced antitumor antibody treatment in the CLL model. These results suggest that AHCC has direct and indirect effects against CLL and that it may be of benefit when combined with existing treatments. Full article

The treatment of advanced unresectable HCC (aHCC) remains a clinical challenge, with limited therapeutic options and poor prognosis. The results of IMbrave150 and HIMALAYA have changed the treatment paradigm for HCC and established immune checkpoint inhibition (ICI), either combined with anti-angiogenic therapy or dual ICI, as preferred first-line therapy for eligible patients with aHCC. Numerous other combination regimens involving ICI are under investigation with the aim of improving the tumour response and survival of patients with all stages of HCC. This review will explore the current evidence for ICI in patients with advanced HCC and discuss future directions, including the unmet clinical need for predictive biomarkers to facilitate patient selection, the effects of cirrhosis aetiology on response to ICI, and the safety of its use in patients with impaired liver function. Full article

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global public health safety and the economy. Multiple antiviral drugs have been developed, and some have received regulatory approval and/or authorization. The use of nutraceuticals can be beneficial for preventing and treating COVID-19 complications. AHCC is a standardized, cultured extract of an edible mushroom Lentinula edodes of the Basidiomycete family of fungi that is enriched in acylated α-1,4-glucans. Here, we evaluated the effects of the oral administration of AHCC on the host response to SARS-CoV-2 infection in two murine models, K18-hACE2 transgenic mice and immunocompetent BALB/c mice. Oral administration of AHCC every other day for one week before and one day post SARS-CoV-2 infection in both strains of mice decreased the viral load and attenuated inflammation in the lungs. AHCC treatment also significantly reduced SARS-CoV-2-induced lethality in the K18-hACE2 mice. AHCC administration enhanced the expansion of γδ T cells in the spleen and lungs before and after viral infection and promoted T helper 1-prone mucosal and systemic T cell responses in both models. In AHCC-fed BALB/c mice, SARS-CoV-2 specific IgG responses were also enhanced. In summary, AHCC supplementation enhances host resistance against mild and severe COVID-19 infection primarily via the promotion of innate and adaptive T cell immune responses in mice. Full article

Sorafenib is currently a targeted agent widely used in the treatment of advanced hepatocellular carcinoma (aHCC). However, to date there is still a lack of a reliable marker capable of predicting sorafenib therapeutic responses. Here, we conducted a genome-wide association study (GWAS) to identify candidate single-nucleotide polymorphism outcome predictors in aHCC patients. A total of 74 real-world sorafenib-treated aHCC patients were enrolled for GWAS and outcome analysis. GWAS showed that rs1010816 (p = 2.2 × 10⁻⁷) was associated with sorafenib therapeutic response in aHCC patients. Kaplan–Meier analysis indicated that the “TT” genotype was significantly associated with a favorable therapeutic response but not significantly associated with overall survival (OS). Univariate followed by multivariate Cox proportional hazard analysis showed that ascites, main portal vein thrombosis, lower platelet count, lower total sorafenib doses, higher PALBI score in model A and higher ALBI grade in model B were significantly associated with a shorter OS. Subgroup analysis showed that only in alcoholic aHCC patients treated by sorafenib, rs1010816 “TT” genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 “TT” genotype. Full article

In recent years, many studies have highlighted the possible close correlation between human diseases and definite patterns of microbial organisms colonizing various organs. Even at sites traditionally considered sterile, such as the upper female reproductive tract (FRT), it is now well-recognized as hosting a low biomass of different bacterial phyla. Additionally, the data from recent studies highlight a possible link between lower and upper FRT dysbiosis with a potential predisposition to cervical and ovarian cancer. Acinetobacter, chlamydia, increased mycoplasma, and lactobacillary scarcity in the upper FRT have all been linked to a predisposition to ovarian cancer. Additionally, a high-diversity vaginal community state type (CST) is linked to the presence and persistence of high-risk human papillomavirus (HPV), resulting in decreased cellular p53 activity and a reduction in the immune activity of T lymphocytes, resulting in cervical and ovarian cancer predisposition. While these findings are still far from being clarified in all aspects, in patients with multiple risk factors for ovarian cancer, a Lactobacillus crispatus treatment with a product with a proven ability to restore a favorable CST should be considered as an add-on therapy. Full article

Atezolizumab plus bevacizumab is the standard of care for first-line systemic therapy for advanced hepatocellular carcinoma (aHCC). Data on the efficacy and safety of atezolizumab plus bevacizumab in patients with aHCC who have received prior systemic therapy are not available. Methods: Patients with aHCC who received atezolizumab plus bevacizumab after at least one systemic treatment between December 2018 and March 2022 were retrospectively identified in 13 centers in Germany and Austria. Patient characteristics, tumor response rates, progression-free survival (PFS), overall survival (OS), and adverse events (AE) were analyzed. Results: A total of 50 patients were identified; 41 (82%) were male. The median age at initiation of treatment with atezolizumab plus bevacizumab was 65 years, 41 (82%) patients had cirrhosis, 30 (73%) Child A, 9 (22%) B, and 2 (5%) C. A total of 34 patients (68%) received atezolizumab plus bevacizumab in the second-line setting and 16 (32%) in later lines. The best radiologic tumor responses were complete remission (2%), partial remission (30%), stable disease (36%), and progressive disease (18%), resulting in an objective response rate of 32% and a disease control rate of 68%. Median OS was 16.0 months (95% confidence interval 5.6–26.4 months), and median PFS was 7.1 months (95% confidence interval 4.4–9.8 months). AE grades 3–4 were observed in seven (14%) and resulted in death in three patients (6%). There were five (10%) bleeding events with a grade ≥ 3, including one (2%) with a fatal outcome. Conclusions: Atezolizumab plus bevacizumab is effective in patients with aHCC who did not have access to this option as first-line therapy. The safety profile was consistent with previous reports. Full article

The high accessibility to healthcare and increasing awareness of hepatocellular carcinoma (HCC) surveillance after sustained virologic response (SVR) to HCV treatment allow early detection of operable HCC in Taiwan. However, the effects of achieving SVR on patient characteristics and surgical outcomes after curative resection remain elusive. We aimed to compare the clinical presentation and postoperative prognosis among patients with early-stage HCV-related HCC and different viral status. We retrospectively analyzed 208 patients with BCLC stage 0 or A-HCC, including 44 patients who remained HCV viremic, 90 patients who developed HCC after achieving SVR (post-SVR HCC), and 74 patients who subsequently achieved SVR after resection. Patients with post-SVR HCC had a lower degree of hepatitis and better liver function than those who achieved SVR or remained viremic after resection. Notably, 75.6% of patients with post-SVR HCC did not have cirrhosis. Patients with post-SVR HCC and those achieving SVR after resection exhibited comparable recurrence rates and recurrence-free survival, while patients with persistent viremia had the worst surgical outcomes. We concluded that patients with post-SVR HCC had a better liver function but similar surgical outcomes compared with patients who achieved SVR after resection. The low prevalence of cirrhosis in patients with post-SVR HCC highlights the importance of regular surveillance after SVR. Full article

Immune checkpoint inhibitors (ICIs) are a key component of different stages of hepatocellular carcinoma (HCC) treatment, particularly in the first line of treatment. A lesson on the primary resistance which hampers their efficacy and activity was learned from the failure of the trials which tested them as first-line mono-therapies. Despite the combination of anti-PD(L)1 agents with anti-VEGF, anti CTLA4, or TKIs demonstrating relevant improvements in efficacy, the “doublets strategy” still shows room for improvement, due to a limited overall survival benefit and a high rate of progressive disease as best response. In this review, we discuss the results from the currently tested doublet strategies (i.e., atezolizumab+bevacizumab, durvalumab+tremelimumab with a mention to the newly presented ICIs/TKIs combinations), which highlight the need for therapeutic improvement. Furthermore, we examine the rationale and provide an overview of the ongoing trials testing the treatment intensification strategy with triplet drugs: anti-PD1+anti-CTLA4+anti-VEGF/TKIs and anti-PD1+anti-VEGF+alternative immunity targets. Lastly, we report on the alternative strategy to integrate ICIs into the new paradigm of immune therapeutics constituted by CAR-T and anti-cancer vaccines. This review provides up-to-date knowledge of ongoing clinical trials of the aforementioned strategies and critical insight into their mechanistic premises. Full article

Sorafenib has been used to treat advanced hepatocellular carcinoma (aHCC). However, there is no evidence for a response of different target lesions to sorafenib administration. Therefore, we aimed to evaluate the effect of sorafenib on various aHCC target lesions. The outcomes of sorafenib treatment on aHCC, i.e., treatment response for all Child A status patients receiving the drug, were analyzed. Of 377 aHCC patients, 73 (19.3%) had complete/partial response to sorafenib, while 134 (35.4%) and 171 (45.2) had a stable or progressive disease, respectively, in the first six months. Of the evaluated metastatic lesions, 149 (39.4%), 48 (12.7%), 123 (32.5%), 98 (25.9%), 83 (22.0%), and 45 (11.9%) were present in liver, bone, lung, portal/hepatic vein thrombus, lymph nodes, and peritoneum, respectively. The overall survival and duration of treatment were 16.9 ± 18.3 and 8.1 ± 10.5 months (with median times of 11.4 and 4.6, respectively). Our analysis showed poor outcomes in macroscopic venous thrombus and bone, higher AFP, and multiple target lesions. ALBI grade A had a better outcome. Sorafenib administration showed good treatment outcomes in selected situations. PD patients with thrombus or multiple metastases should be considered for sorafenib second-line treatment. The ALBI liver function test should be selected as a treatment criterion. Full article

The AHCC standardized extract of cultured Lentinula edodes mycelia, and the standardized extract of Asparagus officinalis stem, trademarked as ETAS, are well known supplements with immunomodulatory and anticancer potential. Several reports have described their therapeutic effects, including antioxidant and anticancer activity and improvement of immune response. In this study we aimed at investigating the effects of a combination of AHCC and ETAS on colorectal cancer cells and biopsies from healthy donors to assess the possible use in patients with colorectal cancer. Our results showed that the combination of AHCC and ETAS was synergistic in inducing a significant decrease in cancer cell growth, compared with single agents. Moreover, the combined treatment induced a significant increase in apoptosis, sparing colonocytes from healthy donors, and was able to induce a strong reduction in migration potential, accompanied by a significant modulation of proteins involved in invasiveness. Finally, combined treatment was able to significantly downregulate LGR5 and Notch1 in SW620 cancer stem cell (CSC) colonospheres. Overall, these findings support the potential therapeutic benefits of the AHCC and ETAS combinatorial treatment for patients with colorectal cancer. Full article

Leishmaniasis is an emerging, uncontrolled, and neglected zoonotic disease. Climate change is contributing to its ongoing global expansion. The dog is the main reservoir; hence the importance of implementing effective treatment, prevention, and control measures in this animal species to protect public health. However, although the standard treatment for canine leishmaniosis (CanL) is effective, it does not provide full parasitological clearance, and side effects and drug resistance have been described. The host’s immune system plays a key role in the establishment and evolution of leishmaniasis. Dietary nucleotides modulate the immune response and, given their reported efficacy and safety in sick and clinically healthy Leishmania-infected dogs and because they represent a sustainable option with no associated side effects or resistance, they could be included within the prevention, treatment, and control strategies for leishmaniasis. This article briefly summarizes the scientific literature on CanL management, including unresolved issues, and reviews the scientific evidence on immunomodulatory effects of dietary nucleotides in different animal species. It also proposes a CanL management algorithm, including nucleotides. It is concluded that nutritional modulation of the immune response with nucleotides can contribute to better management of leishmaniasis following a One Health approach, especially in the COVID-19 era. Full article