Navigating through the PD-1/PDL-1 Landscape: A Systematic Review and Meta-Analysis of Clinical Outcomes in Hepatocellular Carcinoma and Their Influence on Immunotherapy and Tumor Microenvironment.

This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular carcinoma (HCC). Medline, EMBASE, and Cochrane Library database searches were conducted, revealing nine relevant cohort studies (seven PDL-1 and three PD-1). Our meta-analysis showed that PD-1/PDL-1 was a marker of poor survival, regardless of the assessment method (PD-1 overall survival (OS): hazard ratio (HR) 2.40; 95% confidence interval (CI), 1.30-4.42; disease-free survival (DFS): HR 2.12; 95% CI, 1.45-3.10; PDL-1: OS: HR 3.61; 95% CI, 2.75-4.75; and DFS: HR 2.74; 95% CI, 2.09-3.59). Additionally, high level of PD-1/PDL-1 expression was associated with aging, multiple tumors, high alpha-fetoprotein levels, and advanced Barcelona Clinic Liver Cancer stage. This high level significantly predicted a poor prognosis for HCC, suggesting that anti-PD-1 therapy is plausible for patients with HCC. Furthermore, HIF-1 induces PD-1 expression, and PD1lowSOCS3high is associated with a better prognosis. Taken together, combination therapy may be the key to effective immunotherapy. Thus, exploring other markers, such as HIF-1 and SOCS3, along with PD-1/PDL-1 immunotherapy, may lead to improved outcomes.

In Vivo Oncolytic Virotherapy in Murine Models of Hepatocellular Carcinoma: A Systematic Review.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Current therapies often provide marginal survival benefits at the expense of undesirable side effects. Oncolytic viruses represent a novel strategy for the treatment of HCC due to their inherent ability to cause direct tumor cell lysis while sparing normal tissue and their capacity to stimulate potent immune responses directed against uninfected tumor cells and distant metastases. Oncolytic virotherapy (OVT) is a promising cancer treatment, but before it can become a standard option in practice, several challenges-systemic viral delivery optimization/enhancement, inter-tumoral virus dispersion, anti-cancer immunity cross-priming, and lack of artificial model systems-need to be addressed. Addressing these will require an in vivo model that accurately mimics the tumor microenvironment and allows the scientific community to design a more precise and accurate OVT. Due to their close physiologic resemblance to humans, murine cancer models are the likely preferred candidates. To provide an accurate assessment of the current state of in vivo OVT in HCC, we have reviewed a comprehensively searched body of work using murine in vivo HCC models for OVT.

Tumor Budding as a Marker for Poor Prognosis and Epithelial-Mesenchymal Transition in Lung Cancer: A Systematic Review and Meta-Analysis.

Introduction: Currently, tumor budding (TB) is considered to predict the prognosis of patients. The prognostic significance of TB has also been explored in patients with lung cancer, but has not been fully clarified. In the present meta-analysis, we evaluated the prognostic significance, clinicopathological value, and relationship with epithelial-mesenchymal transition (EMT) of TB in lung cancer. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched up to July 7, 2021, for the relevant articles that showed the relationship between TB and prognosis in patients with lung cancer. For statistical analysis, we used pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) to assess the correlation between high-grade TB expression and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), clinicopathological factors, and EMT markers. Results: A total of 3,784 patients from 10 independent studies were included in the statistical analysis. Our results indicated that high-grade TB was significantly associated with poor OS [HR 1.64 (95% CI, 1.43-1.87)] and DFS [HR 1.65 (95% CI, 1.22-2.25)]. In terms of clinicopathological characteristics, high-grade TB was associated with larger tumor size, higher T and N stage, pleural invasion, vascular invasion, lymphatic invasion, and severe nuclear atypia. Interestingly, smoking showed significant association with high-grade TB, despite the fact that previous studies could not show a significant relationship between them. Furthermore, through our systematic analysis, high-grade TB showed a significant relationship with EMT markers. Conclusion: Our findings indicate that high-grade TB is associated with a worse prognosis in patients with lung cancer. TB evaluation should be implemented in routine pathological diagnosis, which may guide the patient's treatment.

Current Trend of Artificial Intelligence Patents in Digital Pathology: A Systematic Evaluation of the Patent Landscape.

The integration of digital pathology (DP) with artificial intelligence (AI) enables faster, more accurate, and thorough diagnoses, leading to more precise personalized treatment. As technology is advancing rapidly, it is critical to understand the current state of AI applications in DP. Therefore, a patent analysis of AI in DP is required to assess the application and publication trends, major assignees, and leaders in the field. We searched five major patent databases, namely, those of the USPTO, EPO, KIPO, JPO, and CNIPA, from 1974 to 2021, using keywords such as DP, AI, machine learning, and deep learning. We discovered 6284 patents, 523 of which were used for trend analyses on time series, international distribution, top assignees; word cloud analysis; and subject category analyses. Patent filing and publication have increased exponentially over the past five years. The United States has published the most patents, followed by China and South Korea (248, 117, and 48, respectively). The top assignees were Paige.AI, Inc. (New York City, NY, USA) and Siemens, Inc. (Munich, Germany) The primary areas were whole-slide imaging, segmentation, classification, and detection. Based on these findings, we expect a surge in DP and AI patent applications focusing on the digitalization of pathological images and AI technologies that support the vital role of pathologists.

Tumor Budding in Gynecologic Cancer as a Marker for Poor Survival: A Systematic Review and Meta-Analysis of the Perspectives of Epithelial-Mesenchymal Transition.

This study aimed to assess the prognostic significance, assessment methods, and molecular features of tumor budding (TB). A literature search of Medline, EMBASE, Cochrane Library, and eleven cohort studies (seven cervical and four endometrial cancers) was conducted. Three assessment methods for TB involving 2009 patients were collected and constituted in the analysis. Our meta-analysis showed that TB was a marker of poor survival, regardless of the cancer origin site or assessment method (overall survival: hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.82-3.17; disease-free survival: HR, 3.32; 95% CI, 2.46-4.48). In endometrial cancers, TB is associated with the epithelial-mesenchymal transition, microvessel density, and decreased hormone receptor expression. Thus, we suggest TB as a poor prognostic marker for all gynecologic cancers.

Development of in-vitro maturation protocol for rat oocytes; under simple culture vs co-culture with cumulus cell monolayer and its developmental potential via Parthenogenetic/artificial activation.

BACKGROUND: Murine is the most abundantly used as laboratory animal models. There has been a tremendous amount of research including; their evolution, growth, physiology, disease modeling as well as genomic mapping. Rats and mice are the most widely used among them. Although both rats and mice fall under the same category still both are different a lot too. As regarding in vitro maturation and development mouse studies are well established as compared to rats which still lies in the early phase of development. So, we tried to figure out rat oocytes in vitro maturation and their developmental potential by performing 3 experiments i.e. superovulation, in vitro Maturation as simple culture (COC's only), and COC's & cumulus cells co-culture, which later further developed using parthenogenetic activation after IVM. Female Sprague Dawley rat 3-4 week used for these studies, we hyper-stimulated their ovaries using PMSG and hCG 150 IU/kg each. After that, we collected ovaries via dissection and retrieved oocytes. We matured them in TCM 199 supplemented with FSH, Estrogen, EGF, and Pyruvate. After maturation, we activated them using two types of activators i.e. Ethanol 7%, Ionomycin. After that, we saw and compared their developmental potential in vitro. RESULTS: Oocytes matured in COC's and Cumulus cell monolayer co-culture (59% ± 4*) showed significantly more even growth and extrusion of the first polar body as compared to the COC's only culture (53.8 ± 7%*). While oocytes activated using Ionomycin showed more promising development until 8 cells/blastocyst level compared to ethanol 7%. CONCLUSION: we concluded that COC's and cumulus monolayer co-culture is better than COC's only culture. Cumulus monolayer provides extra aid in the absorption of nutrients and supplements thus providing a better environment for oocytes growth. Also, we concluded that matured oocytes showed more developmental capacity after activation via ionomycin compared to ethanol.