Universal cost bound of quantum error mitigation based on quantum estimation theory

We present a unified approach to analyzing the cost of various quantum error mitigation methods on the basis of quantum estimation theory. By analyzing the quantum Fisher information matrix of a virtual quantum circuit that effectively represents the operations of quantum error mitigation methods, we derive for a generic layered quantum circuit under a wide class of Markovian noise that, unbiased estimation of an observable encounters an exponential growth with the circuit depth in the lower bound on the measurement cost. Under the global depolarizing noise, we in particular find that the bound can be asymptotically saturated by merely rescaling the measurement results. Moreover, we prove for random circuits with local noise that the cost grows exponentially also with the qubit count. Our numerical simulations support the observation that, even if the circuit has only linear connectivity, such as the brick-wall structure, each noise channel converges to the global depolarizing channel with its strength growing exponentially with the qubit count. This not only implies the exponential growth of cost both with the depth and qubit count, but also validates the rescaling technique for sufficiently deep quantum circuits. Our results contribute to the understanding of the physical limitations of quantum error mitigation and offer a new criterion for evaluating the performance of quantum error mitigation techniques.Comment: 7 + 14 pages, 10 figures. See also a related work by Takagi et al., which appears in the same arXiv posting as arXiv:2208.0917

Ultrastructural Analysis of an Enterolith Composed of Deoxycholic Acid

A 67-year-old Japanese man underwent enterotomy because of enterolith ileus. Component analysis by infrared spectroscopy revealed that the enterolith was composed of a high concentration of deoxycholic acid. We further analyzed and compared the ultrastructure of the enterolith and a commercially available powdered form of deoxycholic acid by means of scanning electron microscopy and energy dispersive X-ray spectroscopy. Energy dispersive X-ray spectroscopy analysis revealed that the ratios of carbon and oxygen in the enterolith were equal to those in the deoxycholic acid powder. Scanning electron microscopy analysis showed rectangular prism-shaped particles on the surface of the enterolith. This structure was similar to that of the deoxycholic acid powder. The surgically removed enterolith had a twisted and coiled appearance. Possible mechanisms underlying the formation of this unique form are discussed

Repeated talaporfin sodium photodynamic therapy for esophageal cancer: safety and efficacy

[Background] Talaporfin sodium photodynamic therapy (tPDT) is an effective salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Repeated tPDT could also be indicated for local recurrence or residue after the first salvage tPDT. However, the safety and efficacy of repeated tPDT have not been elucidated. [Methods] We reviewed 52 patients with esophageal cancer who were treated with the first tPDT at Kyoto University Hospital between October 2015 and April 2020. [Results] Among 52 patients, repeated tPDT after the first tPDT was indicated for 13 patients (25%), of which six had residual tumor, four had local recurrence after complete response (CR) after the first tPDT at the primary site, and six had metachronous lesion. The total session of repeated tPDT was 25; 16 were for primary sites and nine were for metachronous sites. Among them, six patients (46.2%) achieved local (L)-CR and nine lesions (56.3%) achieved lesion L-CR. By session, 10 sessions (40%) achieved L-CR. There were no severe adverse events except for one patient; this patient showed grade 3 esophageal stenosis and perforation after the third tPDT on the same lesion that was previously treated with porfimer sodium photodynamic therapy four times. [Conclusion] Repeated tPDT could be an effective and safe treatment for local failure even after salvage tPDT for esophageal cancer

Inhibition of Rho-associated coiled-coil containing protein kinase enhances the activation of epidermal growth factor receptor in pancreatic cancer cells

<p>Abstract</p> <p>Background</p> <p>Rho-associated coiled-coil containing protein kinase (Rho-kinase/ROCK) is involved in various cellular functions including cell proliferation, and is generally considered to be oncogenic, while some studies show that ROCK functions as a negative regulator of cancer progression. As a result, the precise role of ROCK remains controversial. We have previously reported that Rho-kinase/ROCK negatively regulates epidermal growth factor (EGF)-induced cell proliferation in SW480 colon cancer cells. In the present study, we investigated the role of ROCK in EGF receptor (EGFR) signaling in the pancreatic cancer cell lines, Panc1, KP3 and AsPc1.</p> <p>Results</p> <p>In these cells, Y27632, a specific ROCK inhibitor, enhanced EGF-induced BrdU incorporation. The blockade of EGF stimulation utilizing anti-EGFR-neutralizing antibodies suppressed Panc1 cell proliferation. EGF induced RhoA activity, as well as the phosphorylation of cofilin and myosin light chain (MLC), both targets of ROCK signaling, and Y27632 suppressed both of these processes, indicating that the phosphorylation of cofilin and MLC by EGF occurs through ROCK in Panc1 cells. EGF-induced phosphorylation of EGFR at tyrosine residues was augmented when the cells were pretreated with Y27632 or were subjected to gene silencing using ROCK-siRNA. We also obtained similar results using transforming growth factor-α. In addition, EGF-induced phosphorylation of p44/p42 mitogen-activated protein kinase and Akt were also enhanced by Y27632 or ROCK-siRNA. Moreover, an immunofluorescence microscope study revealed that pretreatment with Y27632 delayed EGF-induced internalization of EGFR. Taken together, these data indicate that ROCK functions to switch off EGFR signaling by promoting the internalization of the EGFR.</p> <p>Conclusions</p> <p>While EGF first stimulates the activation of the EGFR and subsequently increases cancer cell proliferation, EGF concurrently induces the activation of ROCK, which then turns off the activated EGFR pathway via a negative feedback system.</p

Ectopic Breast Cancer Arising within an Axillary Lymph Node

We report our experience with the diagnosis and treatment of an ectopic breast cancer arising within an axillary lymph node. The patient was a 65-year-old woman diagnosed breast cancer and axillary lymph node metastasis. We performed a partial mastectomy and axillary lymph node dissection. Postoperative pathology revealed no malignant lesions in the breast; however, a nodule in one of axillary lymph nodes had mixed benign and malignant components, leading to a diagnosis of invasive ductal carcinoma derived from ectopic mammary tissue. This case represents a very rare form of breast cancer, and the malignancy was difficult to distinguish from metastasis

Prevalence of pathogenic germline variants in the circulating tumor DNA testing

BACKGROUND: Somatic and germline variants are not distinguishable by circulating tumor DNA (ctDNA) testing without analyzing non-tumor samples. Although confirmatory germline testing is clinically relevant, the criteria for selecting presumed germline variants have not been established in ctDNA testing. In the present study, we aimed to evaluate the prevalence of pathogenic germline variants in clinical ctDNA testing through their variant allele fractions (VAFs). METHODS: A total of consecutive 106 patients with advanced solid tumors who underwent ctDNA testing (Guardant360®) between January 2018 and March 2020 were eligible for this study. To verify the origin of pathogenic variants reported in ctDNA testing, germline sequencing was performed using peripheral blood DNA samples archived in the Clinical Bioresource Center in Kyoto University Hospital (Kyoto, Japan) under clinical research settings. RESULTS: Among 223 pathogenic variants reported in ctDNA testing, the median VAF was 0.9% (0.02-81.8%), and 88 variants with ≥ 1% VAFs were analyzed in germline sequencing. Among 25 variants with ≥ 30% VAFs, seven were found in peripheral blood DNA (BRCA2: n = 6, JAK2: n = 1). In contrast, among the 63 variants with VAFs ranging from 1 to < 30%, only one variant was found in peripheral blood DNA (TP53: n = 1). Eventually, this variant with 15.6% VAF was defined to be an acquired variant, because its allelic distribution did not completely link to those of neighboring germline polymorphisms. CONCLUSION: Our current study demonstrated that VAFs values are helpful for selecting presumed germline variants in clinical ctDNA testing

Acquired resistance mechanisms to afatinib in HER2-amplified gastric cancer cells

Cancer treatment, especially that for breast and lung cancer, has entered a new era and continues to evolve, with the development of genome analysis technology and the advent of molecular targeted drugs including tyrosine kinase inhibitors. Nevertheless, acquired drug resistance to molecular targeted drugs is unavoidable, creating a clinically challenging problem. We recently reported the antitumor effect of a pan-HER inhibitor, afatinib, against human epidermal growth factor receptor 2 (HER2)-amplified gastric cancer cells. The purpose of the present study was to identify the mechanisms of acquired afatinib resistance and to investigate the treatment strategies for HER2-amplified gastric cancer cells. Two afatinib-resistant gastric cancer cell lines were established from 2 HER2-amplified cell lines, N87 and SNU216. Subsequently, we investigated the molecular profiles of resistant cells. The activation of the HER2 pathway was downregulated in N87-derived resistant cells, whereas it was upregulated in SNU216-derived resistant cells. In the N87-derived cell line, both MET and AXL were activated, and combination treatment with afatinib and cabozantinib, a multikinase inhibitor that inhibits MET and AXL, suppressed the cell growth of cells with acquired resistance both in vitro and in vivo. In the SNU216-derived cell line, YES1, which is a member of the Src family, was remarkably activated, and dasatinib, a Src inhibitor, exerted a strong antitumor effect in these cells. In conclusion, we identified MET and AXL activation in addition to YES1 activation as novel mechanisms of afatinib resistance in HER2-driven gastric cancer. Our results also indicated that treatment strategies targeting individual mechanisms of resistance are key to overcoming such resistance