Feasibility Study of Transarterial Chemotherapy Followed by Chemoembolization for Recurrent Breast Cancer.

PURPOSE: To assess the treatment response to transarterial chemotherapy followed by chemoembolization for locally recurrent breast cancer. MATERIALS AND METHODS: Thirty-nine women with locally recurrent breast cancer after standard therapy underwent selective intra-arterial chemotherapy followed by embolization using drug-eluting microspheres for locally recurrent tumors and axillary lymph node metastases. Tumor response and toxicity were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and Common Terminology Criteria for Adverse Events (CTCAE), and survival was evaluated by the Kaplan‒Meier method. RESULTS: The local responses of breast tumors at 3 and 6 months were as follows: complete response, 5.1% and 7.2%; partial response, 35.9% and 67.8%; stable disease, 59.0% and 21.4%; and progressive disease, 0.0% and 3.6%, respectively. All adverse events were mild and did not require treatment. The median overall survival (OS) was 46.5 months, and the OS rates for 1 and 2 years were 81.4% and 69.2%, respectively. The size of recurrent tumors and axillary lymph node metastases did not impact prognosis, but both liver and bone metastases adversely affected survival. CONCLUSION: Transarterial chemotherapy followed by chemoembolization may provide a favorable tumor response in patients with locally recurrent breast cancer in whom conventional therapy has failed.

High-density lipoproteins mediate small RNA intercellular communication between dendritic cells and macrophages.

HDL are dynamic transporters of diverse molecular cargo and play critical roles in lipid metabolism and inflammation. We have previously reported that HDL transport both host and nonhost small RNAs (sRNA) based on quantitative PCR and sRNA sequencing approaches; however, these methods require RNA isolation steps which have potential biases and may not isolate certain forms of RNA molecules from samples. HDL have also been reported to accept functional sRNAs from donor macrophages and deliver them to recipient endothelial cells; however, using PCR to trace HDL-sRNA intercellular communication has major limitations. The present study aims to overcome these technical barriers and further understand the pathways involved in HDL-mediated bidirectional flux of sRNAs between immune cells. To overcome these technical limitations, SYTO RNASelect, a lipid-penetrating RNA dye, was used to quantify a) overall HDL-sRNA content, b) bidirectional flux of sRNAs between HDL and immune cells, c) HDL-mediated intercellular communication between immune cells, and d) HDL-mediated RNA export changes in disease. Live cell imaging and loss-of-function assays indicate that the endo-lysosomal system plays a critical role in macrophage storage and export of HDL-sRNAs. These results identify HDL as a substantive mediator of intercellular communication between immune cells and demonstrate the importance of endocytosis for recipient cells of HDL-sRNAs. Utilizing a lipid-penetrating RNA-specific fluorescence dye, we were able to both quantify the absolute concentration of sRNAs transported by HDL and characterize HDL-mediated intercellular RNA transport between immune cells.

[Transarterial Chemoembolization for Unresectable Gastric Cancer in the Esophago-Gastric Junction-A Case Report].

A case of extensive esophageal stenosis and bleeding caused by advanced gastric cancer in esophago-gastric junction treated by the transarterial chemoembolization(TACE)was reported. After standard systemic chemotherapy and radiotherapy, TACE was introduced to control these symptoms. A microcatheter was successfully advanced to the left gastric artery and esophageal artery arising from the thoracic aorta. The blood supply to the lesion was confirmed by CT scan during contrast injection through the microcatheter. The drugs were 5-FU 250 mg/body, cisplatin 20 mg/body, docetaxel 20 mg/body and bevacizumab 100 mg/body. Embolic material was HepaSphereTM(50-100µm). The patient survived one and half years without dysphagia and bleeding. TACE for extensive esophageal stenosis caused by advanced gastric cancer can be a treatment option to control tumor growth and bleeding.

Transarterial management of advance lung cancer.

Previous reports on transarterial treatment for lung cancer were reviewed. The bronchial arterial infusion therapy has a long history since 1964. Better local control with less doses of anti-neoplastic agents was warranted by trying transarterial administration to lung and mediastinal tumors. It is reported that both primary and metastatic tumors are fed by bronchial or other systemic arteries. The bronchial arterial embolization for hemoptysis has been introduced for clinical practice since 1973. Hemoptysis by not only benign but also malignant diseases has been well controlled by embolization. In recent decades, the technical elements for transarterial treatments have markedly improved. They make it possible to carry out precise procedures of selective catheter insertion to the tumor relating arteries. Current concepts of transarterial treatment, technical aspects and treatment outcomes are summarized. Tentative result from chemo-embolization for advanced lung cancer using recent catheter techniques was also described. It provides favorable local control and survival merits. It is considered that a population of lung cancer patients can benefit from transarterial management using small doses of anti-neoplastic agents, with less complications and less medical costs.

[Optimal Clinical Strategy for Photodynamic Therapy Using Liposomal Indocyanine Green-A Case Series Study].

BACKGROUND: The biodistribution of liposomal ICG and the optimal clinical strategy for PDT using liposomal ICG is unclear because of the lack of clinical evidences. PURPOSE: This case-series study aimed to evaluate the biodistribution of liposomal ICG in patients with breast cancer undergoing PDT. METHOD AND RESULT: Four patients with breast cancer underwent PDT with liposomal ICG in addition to a transcatheter arterial chemoembolization(TACE)from August 2020 to October 2020. Patients were administered 300 mg liposomal ICG(180 mg intravenously and 120 mg intratumorally via the feeding artery) 24 hours before PDT during a TACE procedure. We used near-infrared fluorescence(NIR)imaging system(LIGHTVISION®; Shimadzu Corporation)to detect the biodistribution of liposomal ICG. The peak intratumoral liposomal ICG uptake was shown 24 hours after liposomal ICG administration in 3 patients. Only 1 patient had peak uptake at 6 hours, with no uptake at 24 hours. CONCLUSION: NIR-imaging system may be and adjuvant in evaluation of liposomal ICG biodistribution in patients with breast cancer and assisting in the decision-making for the use of PDT with liposomal ICG.

[Microsphere TACE with Arterial Infusion of Bevacizumab for Portal Vein Tumor Thrombus by Hepatocellular Carcinoma].

The successful treatment of 2 cases of portal vein tumor thrombus caused by hepatocellular carcinoma was reported. It is difficult to manage portal vein tumor thrombi by conventional transarterial chemoembolization(c-TACE)using lipiodol and a gelatin sponge. On the other hand, drug-eluting-microsphere TACE(DEM-TACE)can preserve hepatic function by maintaining the capillary circulation of sinusoids and the peribiliary arterial plexus. Even in cases of portal vein tumor thrombus, DEM-TACE could be safely performed without hepatic infarction. Bevacizumab, anti-VGEF monoclonal antibody, was injected into hepatic arteries with anti-neoplastic agents, followed by the epirubicin-loaded superabsorbent polymer microsphere( HepaSphere). The tumor thrombi in 2 cases were successfully eliminated after treatment for more than 2 years without deterioration of the hepatic function.

[Transcatheter Arterial Chemoembolization with HepaSphereTM for Diffuse Liver Metastases from Prostatic Cancer without Elevation of the Serum Prostate-Specific Antigen Level-A Case Report].

Although postoperative recurrence or prostate cancer metastasis is usually accompanied by high prostate-specific antigen (PSA)levels, it may occur even if PSA level is within the normal range. Neuroendocrine differentiation(NED), which is one of such cases, causes rapid disease progression. A man in his 70s underwent total prostatectomy for prostate cancer with high PSA levels. Twenty-two months later, liver, lung, and bone metastases appeared even though the PSA levels were normal. The levels of both neuron-specific enolase and pro-gastrin-releasing peptide were elevated and the patient was clinically diagnosed with NED. Although systemic chemotherapy was administered, the outcome was progressive disease. Transcatheter arterial chemoembolization(TACE)was opted because liver metastases were one of the prognostic factors. Four types of chemotherapy drugs(cisplatin 20 mg, docetaxel 20 mg, 5-FU 250 mg, and bevacizumab 100 mg)were infused through the right and left hepatic arteries, followed by embolization with HepaSphereTM. The liver tumors were remarkably reduced in size and the levels of tumor markers were reduced in 5 sessions. This treatment would avoid the lethal liver trouble; however, the patient died 7 months after the first session of TACE.

[Transcatheter Arterial Chemoembolization with HepaSphereTM for Gastric Cancer with Mediastinal Lymph Node Metastases Causing Esophageal Compression and Dysphagia-A Case Report].

A 50s man was diagnosed with esophagogastric junction cancer. Simultaneously, PET-CT demonstrated mediastinal lymph node metastases. Two months later, 4 courses of systemic chemotherapy(SOX)were provided as preoperative therapy. However, the outcome was PD; therefore, radical gastrectomy could not be performed. Two more months later, esophageal dysphagia developed. Mediastinal lymph nodes that compressed the esophagus and the primary lesion of the cardia were considered to be the causes of dysphagia, and transcatheter arterial chemoembolization targeting those 2 lesions was performed. Cisplatin 20 mg, docetaxel 20 mg, and 5-FU 250mg were the drugs administered. These drugs were injected from the right bronchial artery, left gastric artery, and left phrenic artery, followed by mild embolization with HepaSphereTM. The mediastinal lymph nodes shrunk significantly, and dysphagia improved with 2 sessions. The primary lesion was found to have reduced in size with 6 sessions. Currently, no regrowth of the mediastinal lymph nodes has been observed 16 months(9 sessions) after the first session, and control of the primary lesion has been obtained.

Comparison of the chemokine profiles in the bronchoalveolar lavage fluid between IgG4-related respiratory disease and sarcoidosis: CC-chemokine ligand 1 might be involved in the pathogenesis of sarcoidosis.

BACKGROUND: We previously reported that the cytokine profiles in the bronchoalveolar lavage fluid (BALF) of IgG4-related respiratory disease (IgG4-RRD) more closely resemble the T-helper (Th) 2 response than sarcoidosis. The present study aimed to assess the chemokines in the BALF of IgG4-RRD and sarcoidosis in order to evaluate any possible associations between these chemokines and other markers. METHODS: We examined 12 chemokines using a MILLIPLEX® MAP Kit (Millipore, Darmstadt, Germany) in the same BALF samples of the same 44 patients (IgG4-RRD, n = 11; sarcoidosis, n = 33) in which we had previously evaluated the cytokines. RESULTS: The levels of CC-chemokine ligand (CCL)26 in the BALF of IgG4-RRD patients (median 24.5, range 3.1-401.1 pg/mL) were significantly higher than those in the BALF of sarcoidosis patients (median 3.1, range 3.1-155.6 pg/mL, p < 0.05). Interestingly, the BALF levels of CCL1 in the sarcoidosis patients (median 13.1, range 0.1-106.9 pg/mL) were significantly higher than those of the IgG4-RRD patients (median 9.8, range 0.1-14.7 pg/mL, p < 0.05). Furthermore, the CCL1 levels in the BALF were correlated with the total cell count (ρ = 0.539, p < 0.001), lymphocyte fraction (R = 0.406, P < 0.05), lymphocyte count (R = 0.686, P < 0.001), TNF-α level, (R = 0.748, P < 0.001), and IL-2 level (R = 0.757, P < 0.001) in the BALF of sarcoidosis patients. CONCLUSIONS: CCL1 might reflect disease activity and its involvement in the pathogenesis of sarcoidosis might be more closely related to Th1 than to Th2.

Kososan, a Kampo medicine, prevents a social avoidance behavior and attenuates neuroinflammation in socially defeated mice.

BACKGROUND: Kososan, a Kampo (traditional Japanese herbal) medicine, has been used for the therapy of depressive mood in humans. However, evidence for the antidepressant efficacy of kososan and potential mechanisms are lacking. Recently, it has been recognized that stress triggers neuroinflammation and suppresses adult neurogenesis, leading to depression and anxiety. Here, we examined whether kososan extract affected social behavior in mice exposed to chronic social defeat stress (CSDS), an animal model of prolonged psychosocial stress, and neuroinflammation induced by CSDS. METHODS: In the CSDS paradigm, C57BL/6J mice were exposed to 10 min of social defeat stress from an aggressive CD-1 mouse for 10 consecutive days (days 1-10). Kososan extract (1.0 g/kg) was administered orally once daily for 12 days (days 1-12). On day 11, the social avoidance test was performed to examine depressive- and anxious-like behaviors. To characterize the impacts of kososan on neuroinflammation and adult neurogenesis, immunochemical analyses and ex vivo microglial stimulation assay with lipopolysaccharide (LPS) were performed on days 13-15. RESULTS: Oral administration of kososan extract alleviated social avoidance, depression- and anxiety-like behaviors, caused by CSDS exposure. CSDS exposure resulted in neuroinflammation, as indicated by the increased accumulation of microglia, the resident immune cells of the brain, and their activation in the hippocampus, which was reversed to normal levels by treatment with kososan extract. Additionally, in ex vivo studies, CSDS exposure potentiated the microglial pro-inflammatory response to a subsequent LPS challenge, an effect that was also blunted by kososan extract treatment. Indeed, the modulatory effect of kososan extract on neuroinflammation appears to be due to a hippocampal increase in an anti-inflammatory phenotype of microglia while sparing an increased pro-inflammatory phenotype of microglia caused by CSDS. Moreover, reduced adult hippocampal neurogenesis in defeated mice was recovered by kososan extract treatment. CONCLUSIONS: Our findings suggest that kososan extract prevents a social avoidant behavior in socially defeated mice that is partially mediated by the downregulation of hippocampal neuroinflammation, presumably by the relative increased anti-inflammatory microglia and regulation of adult hippocampal neurogenesis. Our present study also provides novel evidence for the beneficial effects of kososan on depression/anxiety and the possible underlying mechanisms.

Transcatheter Arterial Chemoembolization with Spherical Embolic Agent in Patients with Pulmonary or Mediastinal Metastases from Breast Cancer.

PURPOSE: To evaluate safety and feasibility of transcatheter arterial chemoembolization with superabsorbent polymer microspheres (SAP-MS) for patients with pulmonary or mediastinal metastasis from breast cancer. METHODS: Between November 2002 and January 2015, 14 patients with 29 unresectable pulmonary or mediastinal breast cancer metastases underwent transcatheter arterial chemoembolization using SAP-MS (50-100 µm) after injection of a combination of 2-4 types of anticancer drugs (eg, cisplatin [30 mg] + fluorouracil [500 mg], or epirubicin [40 mg] + mitomycin C [4 mg] + fluorouracil [500 mg]). As a primary endpoint, local tumor response and adverse events were evaluated 1 month after the first transcatheter arterial chemoembolization, according to Response Evaluation Criteria In Solid Tumors Version 1.1 and Common Terminology Criteria for Adverse Events Version 4 criteria. Transcatheter arterial chemoembolization was repeated as needed. Overall survival was analyzed as a secondary endpoint. RESULTS: Response rate was 28.6% (partial response, 4 patients; stable disease, 10 patients). Median progression rate was -12.7%. No cases of hematologic toxicity of grade 3 or higher were observed. A grade 3 maculopapular rash was observed in 1 patient. After the first transcatheter arterial chemoembolization sessions, 63 additional transcatheter arterial chemoembolization sessions were performed (average, 5.5 sessions per patient; range, 2-10 sessions). The median overall survival time after the first session was 29 months, and the 5-year survival rate was 49.5%. CONCLUSIONS: Transcatheter arterial chemoembolization with SAP-MS is a well-tolerated and feasible palliative treatment option for patients with pulmonary or mediastinal metastasis from breast cancer.

[Introduction of Hyperthermia Therapy with Low Dose Systemic Chemotherapy and Hepatic Transarterial Chemo-Embolization for a Case of Advanced Prostatic Cancer].

The case of a 78-year-old man with hormone-independent locally advanced prostatic cancer with liver metastases is reported. Standard systemic chemotherapy was not administered due to his poor general condition. At the initial consultation, rapidly growing liver metastases, multiple lymph node metastases, and extensive locally advanced prostatic lesions were found. Transcatheter arterial chemoembolization, low dose systemic chemotherapy, and thermotherapy were administered. After introduction of this combination therapy, marked regression of all of the lesions, including the liver metastases, lymph node metastases, and pelvic extension was observed. The patient's condition and prognosis were markedly improved without serious complications.

[Transarterial Chemoembolization for Liver Metastasis of Ovarian Malignant Melanoma Resulting in Long-Term Survival].

Melanoma is a potentially aggressive disease, and patients with metastatic melanoma have a poor prognosis, with a median survival of only 6-9 months. There is no effective standard treatment for liver metastasis of malignant melanoma. Primary ovarian malignant melanoma is extremely rare and is usually associated with teratoma. We report a case of malignant melanoma arising in a mature ovarian cystic teratoma that had metastasized to the liver. Six courses of systemic chemotherapy were administered. However, as the liver metastases became enlarged, we performed transarterial chemoembolization(TACE). Following repeated TACE using drug-eluting microspheres for the liver metastasis, the patient survived 80 months from the initial diagnosis.

[A Case of Successful Drug-Eluting Microsphere Transcatheter Arterial Embolization for Hepatocellular Carcinoma with Associated Tumor Thrombus in the Inferior Vena Cava and Right Atrium].

Hepatocellular carcinoma(HCC)with severe vascular invasion has a dismal prognosis, and there is no well-established effective therapy. We report an 84-year-old man who benefited from multiple transcatheter arterial chemoembolization (TACE)treatments for advanced HCC with severe vascular invasion. Initial CT revealed a recurrent, poorly differentiated HCC with tumor thrombus in the inferior vena cava(IVC)and right atrium(Vv3). Two cycles of TACE with 5-FU, DOC, MMC, and superabsorbent polymer microspheres(SAP-MS)with BV resulted in considerable reduction of the tumor thrombus. Tumor markers(PIVKA- / / II)showed remarkable improvement(from 3,803 mAU/mL to 673 mAU/mL). The patient has been alive for 25 months following the appearance of tumor thrombus in the IVC. This case suggests that, in patients with tumor thrombi due to hepatocellular carcinoma, thrombus control and long-term survival are achievable with TACE.

[Abnormal Serum Total Protein Measurement by Lipoprotein-X in an Infant with Biliary Atresia].

Lipoprotein-X (LP-X) in cholestatic jaundice causes abnormal reaction in assays for low-density lipoprotein-cholesterol, but the effects on other test items are unknown. Here, we report an infant with biliary atresia showing abnormal reaction in total serum protein assay using the biuret method, and lipoprotein-X (LP-X) was then detected. In this 11-month-old female infant, jaundice was observed at 2 months old, and a diagnosis of biliary atresia was made. On biochemical tests at 12 months old, the total serum protein concentrations detected by the biuret method were very high, and the response curve and linearity of dilution were abnormal. LP-X was detected by agar electrophoresis. In addition and recovery experiments with normal serum fractionation of the patient's LP-X-rich lipoprotein fraction prepared by ultracentrifugation, normal γ-globulin fractionation showed an abnormal reaction by the biuret method. In infants with biliary atresia, we showed that the total serum protein assay by the biuret method was influenced by LP-X-rich lipoprotein, which may be caused by abnormal reaction of LP-X and γ-globulin. [Case Report].

[Trans-Arterial Chemoembolization Therapy for Refractory Advanced Non-Small Cell Lung Cancer with Spherical Embolic Material--A Single Case Report].

Here, we report the use of trans-arterial chemoembolization for primary lung cancer. The patient was a 56-year-old woman with refractory Stage Ⅳ non-small cell lung cancer who had been treated with repeated systemic chemotherapy. The primary lesion in the right lower lobe was 75 mm in size, with multiple lung metastases. It invaded the right main bronchus and caused severe cough. Radiotherapy was not indicated because of the size and extent of the lesion. During a period of 6 months, chemoembolization of the bilateral bronchial arteries using cisplatin 20 mg, docetaxel 20 mg, and 5-FU 250 mg with HepaSphere (super-absorbent polymer microspheres) was performed 5 times. Twenty mg of docetaxel was loaded onto 25 mg of HepaSphere. The microspheres were between 50 and 100 microns in the dry state. The endpoint of embolization was not stasis but the reduction of arterial flow. There were no serious complications during or after the procedure. Immediately after the first session, the patient's cough was significantly improved. After 5 sessions of the same treatment, the primary lesion was reduced to 48 mm and the level of CEA was reduced from 9.8 to 4.3 ng/mL. The invasion to the right main bronchus was reduced. The patient has been well without any symptoms for 9 months after initiation of trans-arterial chemoembolization.

[Transcatheter Arterial Chemoembolization with Super absorbent Polymer Microspheres for a Large Lung Cystic Adenocarcinoma in the Left Pulmonary Cavity].

A 57-year-old woman presented with lung adenocarcinoma and carcinomatous pleurisy in January 2013. The primary lesion had been treated with 60-Gy radiation therapy. She, however, showed a recurrence of the tumor in her pulmonary cavity. She received systemic chemotherapy for 1 year but did not show any improvement. She visited our clinic in March 2014. Her performance level was 3. Her hemoglobin level was 8.5 g/dL. The CT scan showed that the size of the cystic tumor was 200 × 144 × 143 mm. The tumor severely compressed her heart. We performed TACE using a spherical embolic agent. The microcatheter was guided through the left bronchial artery; left intercostal artery 9, 10, and 11; and the left inferior phrenic artery. The anticancer drugs selected were CDDP and 5-FU. The embolic material used was SAP-MS. After 3 therapy sessions, the CT scan showed shrinkage of the target lesion to 100 × 93 × 54 mm. Her hemoglobin level increased to 13.8 g/dL; furthermore, the severity of dyspnea decreased, and she showed a performance status of 0. TACE with SAP-MS was successfully performed for the large cystic tumor in the pulmonary cavity that metastasized from the lung cancer and was refractory to standard treatments. After the treatment, the tumor size decreased and the patient's symptoms alleviated.

Local control and prognostic significance of transarterial treatment for limited recurrence of ovarian cancer as third-line and beyond therapy.

BACKGROUND: We aimed to retrospectively evaluate the safety and efficacy of transarterial treatment for the recurrence of ovarian cancer, limited to one or two gross regions, in a palliative setting as third-line and beyond therapy. METHODS: Twenty-six consecutive patients were enrolled to undergo transarterial treatment of target lesions that were life-threatening or influenced their quality of life. Transarterial infusion via each feeding artery using 20-40 mg cisplatin and 20-40 mg docetaxel per patient was repeated every 4-6 weeks. Superabsorbent polymer microspheres were added for embolization after drug infusion, especially in hepatic or pelvic treatments. Univariate and multivariate Cox's proportional hazards models were used to assess the correlations between overall survival and individual parameters. RESULTS: A total of 63 feeding arteries (median 2 per patient; range 1-5) were treated for 36 target sites (liver, 12; pelvis, 8; abdominal cavity, 7; lymph node, 3; other, 6) at the initial treatment. Of the 128 total sessions, the only grade 3/4 toxicity was neutropenia (3.8 %). The target lesion response rate by RECIST ver.1.1 was 50.0 % (11.5 % complete response; 38.5 % partial response). After a median follow-up of 30 months, the median overall survival was 16 months. Among 10 tumor-associated symptomatic patients, 7 showed symptom improvement. Multivariate analyses shows that the only independent prognostic factor was target lesion response (hazard ratio 18.7; 95 % CI 1.9-183.4; p = 0.01). CONCLUSIONS: Transarterial treatment for ovarian cancer achieves a high local response and good symptom control, and significantly contributes to survival for patients with local control after multiple relapses.

Low serum carnitine level is associated with increased urinary carnitine excretion in late pregnancy.

BACKGROUND: Carnitine is essential for fatty acid metabolism. Free carnitine (FCA) is excreted in the urine in the glomerulus, but is partly reabsorbed by a carnitine transporter. The mechanism underlying the decrease in serum carnitine level during pregnancy is unclear. OBJECTIVE: To investigate whether low carnitine level is associated with increased renal excretion in pregnant women. METHODS: We recruited 43 healthy pregnant and 25 non-pregnant women. Total carnitine (TCA) and FCA levels were measured using the enzymatic cycling method, and the acylcarnitine (ACA) level was calculated. Fractional excretion (FE) was calculated as carnitine clearance divided by creatinine clearance. RESULTS: The mean TCA, FCA, and ACA levels were lower at 12 weeks of gestation in pregnant than non-pregnant women (P < .001); the levels decreased further at 36 weeks, reaching 39%, 36%, and 52% of those in non-pregnant women, respectively (P < .001). The FEs were 3-4-fold higher in pregnant women than non-pregnant women. Pregnant women had a lower serum FCA/TCA ratio than non-pregnant women (0.788 ± 0.098 vs 0.830 ± 0.074, respectively; P < .05), whereas the urine FCA/TCA ratio was similar between the groups. CONCLUSION: Low carnitine level is associated with increased renal excretion during late pregnancy.

High-speed classification of coherent X-ray diffraction patterns on the K computer for high-resolution single biomolecule imaging.

Single-particle coherent X-ray diffraction imaging using an X-ray free-electron laser has the potential to reveal the three-dimensional structure of a biological supra-molecule at sub-nanometer resolution. In order to realise this method, it is necessary to analyze as many as 1 × 10(6) noisy X-ray diffraction patterns, each for an unknown random target orientation. To cope with the severe quantum noise, patterns need to be classified according to their similarities and average similar patterns to improve the signal-to-noise ratio. A high-speed scalable scheme has been developed to carry out classification on the K computer, a 10PFLOPS supercomputer at RIKEN Advanced Institute for Computational Science. It is designed to work on the real-time basis with the experimental diffraction pattern collection at the X-ray free-electron laser facility SACLA so that the result of classification can be feedback for optimizing experimental parameters during the experiment. The present status of our effort developing the system and also a result of application to a set of simulated diffraction patterns is reported. About 1 × 10(6) diffraction patterns were successfully classificatied by running 255 separate 1 h jobs in 385-node mode.