Gingival Blood Flow Velocity by Video Capillaroscopy as an Indicator of Gingival Inflammation.

Purpose: We evaluated the usefulness of gingival capillary blood flow velocity (BFV) as an indicator of inflammation in the gingival sulcus.

Methods: Twenty-two non-smoking female dental hygiene students from Aichi Gakuin University Junior College in Nagoya, Japan, with no medication use were assessed for periodontal, gingival blood flow, and nutrient intake. Gingival blood flow was recorded by video capillaroscopy (GOKO-Bscan-ZD).

Pharmacokinomic Profiling Using Patient-Derived Cell Lines Predicts Sensitivity to Imatinib in Dermatofibrosarcoma Protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma, characterized by a fusion. Imatinib, a multi-target tyrosine kinase inhibitor, is a standard treatment of DFSP. However, resistance emerges in 10-50% of cases.

Impact of Sensitive Circulating Tumor DNA Monitoring on CT Scan Intervals During Postoperative Colorectal Cancer Surveillance.

Objective: This study investigated whether digital polymerase chain reaction (dPCR)-based circulating tumor DNA (ctDNA) monitoring can allow longer intervals between computed tomography (CT) scans during postoperative surveillance of colorectal cancer (CRC).

Background: Practical guidelines still recommend intensive postoperative surveillance of CRC using periodical CT scans and serum carcinoembryonic antigen testing.

Methods: The longitudinal dynamics of ctDNA for 52 patients with CRC as measured by dPCR using probes targeting 87 individual tumor-specific mutations (1-5 per patient) were compared with results from conventional (ie, clinical) surveillance using serum tumor markers and CT.

The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment.

Regulatory T (Treg) cells play key roles in cancer immunity by suppressing a range of antitumor immune responses and contributing to resistance to PD-1 blockade therapy. Given their critical roles in self-tolerance, local control of immunosuppression by Treg cells, such as in the tumor microenvironment, has been intensively studied. Inhibition of HSP90, a chaperone with vital roles in regulating proteostasis in cancer cells, impedes cancer progression by interrupting oncogenic signaling pathways and potentially modulating antitumor immunity, but we have very little mechanistic insight into these immune modulatory effects.

Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations.

Background: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case.

Establishment and characterization of multiple patient-derived organoids from a case of advanced endometrial cancer.

Patient-derived organoids (PDOs) retain the original tumor's characteristics to a large degree and allow direct evaluation of the drug sensitivity, thereby emerging as a valuable resource for both basic and preclinical researches. Whereas most past studies stereotypically adopted a single PDO as an avatar of the patient, it remains to be investigated whether this assumption can be justified even for the tumor with spatial diversity. To address this issue, we established and characterized multiple PDOs originating from various sites of a patient with advanced uterine carcinosarcoma (UCS).

Harnessing the potential of reverse-phase protein array technology: Advancing precision oncology strategies.

The last few decades have seen remarkable strides in the field of cancer therapy. Precision oncology coupled with comprehensive genomic profiling has become routine clinical practice for solid tumors, the advent of immune checkpoint inhibitors has transformed the landscape of oncology treatment, and the number of cancer drug approvals has continued to increase. Nevertheless, the application of genomics-driven precision oncology has thus far benefited only 10%-20% of cancer patients, leaving the majority without matched treatment options.

Intracellular stress caused by composite resins: An study using a bioluminescent antioxidant-responsive element reporter assay.

Context: Elucidating the effects of leachates from composite resins (CRs) on cells by examining the transcription level of detoxification genes and the antioxidant-responsive element (ARE), would be helpful in clinical practice.

Aims: The aim of the study is to investigate the cytotoxicity of commercially available CRs, we used a reporter assay system to evaluate intracellular stress based on ARE-mediated transcription.

Setting And Design: The study design was an study.

Stromal Reprogramming through Dual PDGFRα/β Blockade Boosts the Efficacy of Anti-PD-1 Immunotherapy in Fibrotic Tumors.

Unlabelled: Excess stroma and cancer-associated fibroblasts (CAF) enhance cancer progression and facilitate immune evasion. Insights into the mechanisms by which the stroma manipulates the immune microenvironment could help improve cancer treatment. Here, we aimed to elucidate potential approaches for stromal reprogramming and improved cancer immunotherapy.

Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer.

We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment.

Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer.

We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses was evaluated by the ratio of the variant allele frequency of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis.

Pharmacological blockage of transforming growth factor-β signalling by a Traf2- and Nck-interacting kinase inhibitor, NCB-0846.

Background: Metastasis is the primary cause of death in cancer patients, and its management is still a major challenge. Epithelial to mesenchymal transition (EMT) has been implicated in the process of cancer metastasis, and its pharmacological interference holds therapeutic promise.

Methods: Traf2- and Nck-interacting kinase (TNIK) functions as a transcriptional coregulator of Wnt target genes.

Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing β1 Integrin, Enhancing Drug Resistance.

Extracellular vesicles (EV) from cancer-associated fibroblasts (CAF) are composed of diverse payloads. Although CAFs impact the aggressive characteristics of gastric cancer cells, the contribution of CAF-EV to gastric cancer progression has not been elucidated. Here, we investigated the molecular mechanism of the changes in gastric cancer characteristics induced by CAF-EV.

Feasibility of Targeting Traf2-and-Nck-Interacting Kinase in Synovial Sarcoma.

Background: The treatment of patients with metastatic synovial sarcoma is still challenging, and the development of new molecular therapeutics is desirable. Dysregulation of Wnt signaling has been implicated in synovial sarcoma. Traf2-and-Nck-interacting kinase (TNIK) is an essential transcriptional co-regulator of Wnt target genes.

Prognostic impact of ACTN4 gene copy number alteration in hormone receptor-positive, HER2-negative, node-negative invasive breast carcinoma.

Background: Most patients with hormone receptor (HR)-positive, human epidermal growth factor receptor type 2 (HER2)-negative breast cancer can be cured by surgery and endocrine therapy, but a significant proportion suffer recurrences. Actinin-4 is associated with cancer invasion and metastasis, and its genetic alteration may be used for breast cancer prognostication.

Methods: The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridisation (FISH) in two independent cohorts totalling 597 patients (336 from Japan and 261 from the USA) with HR-positive, HER2-negative, node-negative breast cancer.

Utility of Reverse-Phase Protein Array for Refining Precision Oncology.

Despite the early successes of targeted therapies and continuous improvements in next-generation sequencing technology over the last two decades, genomics-driven precision oncology has helped only a minority of cancer patients; thus treatment regimens are still not matched to the vast majority of cancer patients. It has become apparent that genomic profiling in itself is limited with respect to optimal selection of patients for targeted therapy. Proteomics-based approaches (in contrast to genomics-based and transcriptomics-based approaches) capture biological processes (e.

Signaling pathway profiling using reverse-phase protein array and its clinical applications.

Increased accessibility to next-generation sequencing within the last decade has led to a paradigm shift in cancer treatment from one-size-fits-all medicine to precision medicine providing therapeutic strategies tailored to the requirements of individual patients. However, the effect of even the most successful agent yet tested is only transient, and durable efficacy has yet to be achieved. Genome- and transcriptome-based approaches cannot fully predict the diversity of protein expression patterns or post-translational modifications that directly contribute to cancer pathogenesis and physiology.

Emergence of TNIK inhibitors in cancer therapeutics.

The outcome of patients with metastatic colorectal cancer remains unsatisfactory. To improve patient prognosis, it will be necessary to identify new drug targets based on molecules that are essential for colorectal carcinogenesis, and to develop therapeutics that target such molecules. The great majority of colorectal cancers (>90%) have mutations in at least one Wnt signaling pathway gene.

TNIK inhibition abrogates colorectal cancer stemness.

Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik(-/-)/Apc(min/+) mutant mice develop significantly fewer intestinal tumours.

Therapeutic targets in the Wnt signaling pathway: Feasibility of targeting TNIK in colorectal cancer.

The genetic and epigenetic alterations occurring during the course of multistage colorectal carcinogenesis have been extensively studied in the last few decades. One of the most notable findings is that the great majority of colorectal cancers (>80%) have mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. Loss of functional APC protein results in activation of canonical Wnt/β-catanin signaling and initiates intestinal carcinogenesis.