Successful treatment with nivolumab in a patient with unresectable oral squamous cell carcinoma following ineffective chemoradiotherapy.

Key Clinical Message: Nivolumab has been clinically successful in prolonging the overall survival of patients with recurrent and metastatic head and neck cancer, complete remission is rare. Synergistic combinations of immunotherapy and conventional cancer treatments, such as radiotherapy or chemotherapy, are likely to be the most viable strategies for improving patient responses.

Abstract: Immune checkpoint inhibitors have revolutionized recurrent, metastatic oral cancer treatment; however complete remission in advanced stages is unusual.

Structure-guided optimisation of -hydroxythiazole-derived inhibitors of factor inhibiting hypoxia-inducible factor-α.

The human 2-oxoglutarate (2OG)- and Fe(ii)-dependent oxygenases factor inhibiting hypoxia-inducible factor-α (FIH) and HIF-α prolyl residue hydroxylases 1-3 (PHD1-3) regulate the response to hypoxia in humans catalysing hydroxylation of the α-subunits of the hypoxia-inducible factors (HIFs). Small-molecule PHD inhibitors are used for anaemia treatment; by contrast, few selective inhibitors of FIH have been reported, despite their potential to regulate the hypoxic response, either alone or in combination with PHD inhibition. We report molecular, biophysical, and cellular evidence that the -hydroxythiazole scaffold, reported to inhibit PHD2, is a useful broad spectrum 2OG oxygenase inhibitor scaffold, the inhibition potential of which can be tuned to achieve selective FIH inhibition.

Human Oxygenase Variants Employing a Single Protein Fe Ligand Are Catalytically Active.

Aspartate/asparagine-β-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and Fe oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor-like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate Fe rather than the typical triad of two histidine and one glutamate/aspartate residue. We report kinetic, inhibition, and crystallographic studies concerning human AspH variants in which either of its Fe binding histidine residues are substituted for alanine.

Lac water extract inhibits IFN-γ signaling through JAK2-STAT1-IRF1 axis in human melanoma.

Interferon-γ (IFN-γ) is a cytokine that plays an important role in the host defense of infectious diseases and in immune surveillance during tumor development; however, it has adverse effects in the pathogenesis of autoimmune diseases and in immunosuppressive microenvironments, promoting the immunoevasion of cancer cells. In this study, we identified lac water extract (Lac) as a candidate that can suppress IFN-γ signaling amongst 112 types of natural products, using PD-L1 promoter as a readout for the IFN-γ signaling. Moreover, we determined that Lac inhibits IFN-γ-induced PD-L1 and MHC class I expression on the cell surface in melanoma cells, both of which have been identified as the downstream molecules of IFN-γ signaling.

Perforation of intramural gastric metastasis during preoperative chemotherapy in a patient with thoracic esophageal squamous cell carcinoma.

Introduction: Perforation of intramural metastasis to the stomach (IMS) from esophageal cancer during chemotherapy has not been reported.

Presentation Of Case: A 68-year-old male consulted our hospital due to appetite loss. He was diagnosed with advanced esophageal squamous cell carcinoma in the lower thoracic esophagus along with a large IMS in the upper stomach.

Bone metastasis in gastrointestinal stromal tumors preferentially occurs in patients with original tumors in sites other than the stomach.

Bone metastases are rare in gastrointestinal stromal tumors (GISTs) and data on the clinicopathological profiles are lacking. The purpose of this report was to identify the clinicopathological profiles of this rare clinical setting by evaluating 23 cases, four of which were our own and the additional 19 were from the relevant English literature. In 18 cases, the primary GISTs occurred in sites other than the stomach, although a high proportion of these tumors do arise in the stomach.

Measuring and evaluating morphological asymmetry in fish: distinct lateral dimorphism in the jaws of scale-eating cichlids.

The left-right asymmetry of scale-eating Tanganyikan cichlids is described as a unilateral topographical shift of the quadratomandibular joints. This morphological laterality has a genetic basis and has therefore been used as a model for studying negative frequency-dependent selection and the resulting oscillation in frequencies of two genotypes, lefty and righty, in a population. This study aims were to confirm this laterality in Perissodus microlepis Boulenger and P.

Observation of spermatozoa by a high-magnification microscope.

Semen analyses are the primary tool for evaluating male infertility, as semen parameters are useful for predicting potential fertility. In the field of assisted reproductive technology (ART), the single best motile spermatozoon should be selected, especially when performing intracytoplasmic sperm injection (ICSI). In this context, the motile sperm organelle morphology examination (MSOME) was developed as a method of assessing the detailed morphology of motile spermatozoa in real time at a magnification of up to 6,300× on a video system.

Testicular volume discrepancy is associated with decreased semen quality in infertile Japanese males with varicoceles.

Purpose: We retrospectively reviewed infertile Japanese males for testicular volume discrepancies (D) and semen parameters to evaluate whether left grade II-III varicoceles (V) cause testicular damage.

Methods: Seventy-seven patients who had idiopathic male infertility and 88 who had V without other causes of infertility were examined. We excluded cases of azoospermia.

Hematospermia: etiology, diagnosis, and treatment.

Hematospermia is a relatively frequent, distressing, and frightening symptom for the majority of men. Although the differential diagnosis list is extensive, it is usually a benign, self-limiting disorder, including inflammatory and infective pathologies, resolving in several weeks. However, in some cases, hematospermia is the harbinger of more serious pathological lesions that should not be missed.