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Colorectal cancer is the third most common cancer globally, and the poor prognosis of patients with metastatic colorectal cancer (mCRC) warrants urgent attention. We previously obtained 10 candidate serum biomarkers for mCRC. Our aim with this study was to determine the prognostic performance of the pre-treatment serum C-C motif chemokine ligand 7 (CCL7) concentration in patients with mCRC.Protein concentrations of CCL7 were examined using ELISA and immunohistochemistry for serum (n=110) and surgical specimens (n=85), respectively, of patients with mCRC. The relationship between protein concentration and prognosis was examined using Cox regression analysis, receiver operator characteristic curve analysis and the Kaplan-Meier method.The overall survival (OS) of patients with high concentrations of serum CCL7 was significantly poorer than that of patients with low concentrations. Patients with a high CCL7 concentration in the stroma had significantly poorer outcomes than those with a low concentration. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 were significantly higher in the high-CCL7 group, compared to those in the low-CCL7 group. Univariate and multivariate analysis revealed that serum CCL7 concentration was a significant prognostic factor for mCRC. The combination of serum CCL and CEA concentrations was also useful in this regard (area under the curve=0.71).The combined pre-treatment serum levels of CCL7 and CEA are useful prognostic biomarkers for mCRC.

Cancer immunotherapy including immune checkpoint inhibitors(ICIs)have established itself as the fourth cancer therapy. However, the response rate of ICIs is still only about 20%, and tumors resistant to ICIs are often so-called"cold-tumor"with low tumor immunogenicity. Therefore, research and development is being conducted worldwide on how to convert cold- tumors into hot-tumors with high immunogenicity. In this paper, we review the relationship between tumor immunogenicity and ICI, as well as therapeutic methods to enhance tumor immunogenicity, and introduce our research about novel cancer peptide vaccination therapy.

The preoperative prognostic nutritional index (PNI) calculated based on the serum albumin concentration and peripheral blood lymphocyte count has been reported to correlate with the prognosis in patients undergoing cancer surgery. However, in case of very old patients over 85 years old, the value of preoperative PNI in colorectal cancer has not been studied in any detail. The aim of this study was to assess the PNI as a predictor of postoperative outcome in elderly patients over 85 years old with colorectal cancer. We performed a retrospective review in forty-five patients over 85 years old who underwent colorectal tumor resection at our hospital from April 2013 to March 2018. The correlations between preoperative PNI and postoperative complications were examined. The incidence rate of postoperative complications was 31.1% (14/45). All of cases with postoperative complications were improved conservatively. The median preoperative PNI was 43.20 (range 24.05–57.05) in the validation study. According to the receiver operating characteristic (ROC) curve, cutoff value of PNI was set at 45.0 in the validation study. An univariate analysis demonstrated that PNI (p = 0.0006), operation style (elective/emergency) (p = 0.03), operation approach (open/laparoscopy) (p = 0.03), and T factor (p = 0.04). A multivariate analysis showed that PNI was independent predictive factor of postoperative complications. Moreover 3-year overall survival rates of patients in the PNI ≧ 45 and PNI p = 0.009). This study suggested that PNI is a pivotal independent predictor of the postoperative outcome among elderly patients over 85 years old after colorectal cancer surgery.

A 49-year-old man came to our department for the purpose of scrutinizing liver tumor. CA19-9 and CA125 increased, and AFP and PIVKA-Ⅱ were within the normal range. CT showed a large number of early ring enhanced tumor, and a tumor thrombus in the left branch of the portal vein. Tumor biopsy revealed adenocarcinoma. Chemotherapy(gemcitabine, cisplatin plus S-1: GCS)was performed for intrahepatic cholangiocarcinoma(r/o combined hepatocellular carcinoma and cholangiocarcinoma). Lenvatinib was administered because portal vein tumor thrombus and PIVKA-Ⅱ increased after GCS therapy. Two months later, CA19-9 and PIVKA-Ⅱ were decreased and portal vein tumor thrombus was shrunk. Extended left hepatectomy was performed for the purpose of disease control. Histopathological examination revealed some hepatocellular carcinoma components in intrahepatic cholangiocarcinoma. Tumor thrombus was vitrified and necrotic. After hepatectomy, administration of lenvatinib was continued for the residual lesion, and no significant tumor growth was observed.

This study reports a case of a 61-year-old man with a chief complaint of anemia. The patient was diagnosed with esophageal cancer(Stage Ⅰ). Preoperative examination revealed alcoholic liver cirrhosis(Child-Pugh A, liver damage B). After a period of abstinence to improve liver function, minimally invasive esophagectomy, retrosternal reconstruction with a gastric tube, and two-field lymph node dissection were performed. The thoracic duct was preserved during the operation. Post- surgery, the bill pleural effusion was increased. Drainage was initiated using thoracentesis with frosemide, spironolactone, and tolvaptan. On post-operating day(POD)35, the patient was discharged; however, right pleural effusion continued to increase. Therefore, cell-free and concentrated reinfusion therapy for right pleural effusion was performed on POD 56. After the treatment, the pleural effusion was well-controlled with 20 mg of frosemide. This case suggested that cell-free and concentrated pleural effusion reinfusion therapy contributed to the management of refractory pleural effusion in patients with esophageal cancer accompanied by cirrhosis.

This case pertains to a female patient in her 60s who was diagnosed with carcinoma in the cecum with lung, ovarian, and peritoneal metastases. She complained of abdominal distension and poor feeding because her ascites and ovarian metastasis worsened 18 months after chemotherapy initiation. Repeated cytologic examination of the ascitic fluid revealed no malignant cells. Therefore, Pseudo-Meigs' syndrome was suspected. Bilateral salpingo-oophorectomy was performed as palliative surgery because of the patient's reduced capacity to perform activities of daily living(ADL)due to ascites. After palliative surgery, her ascites disappeared, and she was able to better perform ADL. Further, chemotherapy was resumed. The patient remains well 10 months after surgery. This case highlights the importance of considering Pseudo-Meigs' syndrome in patients with massive ascites and ovarian metastasis, because surgical resection can improve their quality of life.

An 80 year-old woman with anorexia and jaundice was diagnosed with mass-forming intrahepatic cholangiocarcinoma, lymph node metastasis, common hepatic duct strictures, and obstructive jaundice. PET-CT showed FDG accumulation in the primary lesion(SUVmax 19.0)and swollen lymph nodes. Her ADL and major organ functions were judged to be sufficient for treatment. After treatment for jaundice, she received a total of 6 courses of gemcitabine, cisplatin plus S-1(GCS)therapy as neoadjuvant chemotherapy(NAC). Her first treatment was an 80% dose of GCS, but she was subsequently diagnosed with Grade 4 thrombocytopenia(CTCAE v5.0). The dose of gemcitabine was further reduced, and no adverse events of Grade 3 or higher were observed thereafter. After NAC, PET-CT showed decreased FDG accumulation in the primary lesion(SUVmax 3.3)and normalization of FDG accumulation in the lymph nodes. Extended right hepatectomy and biliary reconstruction were performed as radical resection(R0). The final diagnosis was pT2, N0, M0, Stage Ⅱ. After hepatectomy, her anorexia and poor ADL persisted. She was discharged to her home 151 days after her surgery.

Although the current standard of care for patients with lower rectal cancer in Japan includes total mesorectal resection with lateral lymph node dissection, postoperative local and distant recurrence rates are high. Multidisciplinary treatment is important to improve the prognosis. A man in his 30s was diagnosed with lower rectal cancer due to bloody stool and referred to our department. He was diagnosed as cT3N3M0, cStage Ⅲc with right obturator lymph node metastasis. Four courses of neoadjuvant chemotherapy(NAC)with FOLFOXIRI plus cetuximab were performed. Because Grade 3 neutropenia was observed in the first cycle(CTCAE v5.0), pegfilgrastim was administered in the second and subsequent cycles, and NAC was completed without dose reduction. The patient underwent laparoscopy-assisted intersphincteric rectal resection and D3+rtLD2 dissection. Histopathological resection margins were negative, and the resection was R0. Lymph node metastasis was found only in No. 263d-rt, and the pathological diagnosis was ypT3N3M0, pStage Ⅲc. Histological evaluation of response to treatment was Grade 2. The postoperative course was good and the patient was discharged on postoperative day 15. The patient received 8 courses of adjuvant chemotherapy with mFOLFOX6 from the 7th postoperative week and is alive and recurrence-free 6 months after surgery.

Background Cancer stem cells (CSCs) are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) which possess enhanced chemoresistance and metastatic potential. To enable the development of targeted therapy against CSLCs, we identified a gene responsible for this phenotype in CSLC. Methods Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique sphere inducing medium, and HuH-7 cells were used as non-sphere forming cells in the same condition. RNA-sequencing was performed followed by validation with quantitative RT-PCR and western blotting. Knockdown experiments were done by using CRISPR-Cas9 genome-editing, and the rescue experiments were performed using the expressing plasmid vector. Chemoresistance and liver metastasis of the cells, was studied following the splenic injection of cells to severely immune deficient mice and evaluated using the MTS assay. Quantification of exosomes in the medium was done using ELISA. Results RAB3B was identified as an up-regulated gene in both CSLCs and prognostically poor hepatocellular carcinoma (HCC) by RNA-sequencing. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion was observed in CSLCs, and it was not observed in the RAB3B-KD cells. In addition, the RAB3B expression correlated with the expression of ABCG2, APOE, LEPR, LXN, and TSPAN13. Conclusion The up regulation of RAB3B may play an important role in the chemoresistance and metastatic potential of CSLCs.

Despite previous intensive investigations on epiblast cell migration in avian embryos during primitive streak development before stage (st.) 4, this migration at later stages of brain development has remained uninvestigated. By live imaging of epiblast cells sparsely labeled with green fluorescence protein, we investigated anterior epiblast cell migration to form individual brain portions. Anterior epiblast cells from a broad area migrated collectively towards the head axis during st. 5-7 at a rate of 70-110 µm/h, changing directions from diagonal to parallel and forming the brain portions and abutting head ectoderm. This analysis revised the previously published head portion precursor map in anterior epiblasts at st. 4/5. Grafting outside the brain precursor region of mCherry-expressing nodes producing anterior mesendoderm (AME) or isolated AME tissues elicited new cell migration towards ectopic AME tissues. These locally convergent cells developed into secondary brains with portions that depended on the ectopic AME position in the anterior epiblast. Thus, anterior epiblast cells are bipotent for brain/head ectoderm development with given brain portion specificities. A brain portion potential map is proposed, also accounting for previous observations.

A 67-year-old woman was admitted with melena. A colonoscopy detected a 50 mm submucosal tumor close to the dentate line. We diagnosed the rectal gastrointestinal stromal tumor by EUS-FNA. With the expectation of tumor shrinkage and strong hope of the patient, we started imatinib mesylate as neoadjuvant chemotherapy. A CT scan after 3 months after administration of imatinib mesylate showed the reduction of the size to 35 mm. We operated transanal endoscopic surgery considering the localization of the tumor. From histopathological findings, the tumor was low risk in the modified-Fletcher classification, and low risk in the Miettinen classification. Eight months after the operation, no recurrence was observed without further adjuvant chemotherapy. In this case, we were able to resect the tumor without injuring the film of tumor by operating transanal endoscopic surgery, because of tumor shrinkage with imatinib mesylate as neoadjuvant chemotherapy. I considered that using imatinib mesylate preoperatively was contributed to minimally invasive surgery.

Patient is 69-year-old man, who underwent a high anterior resection with laparoscopic support for rectal cancer. The patient was diagnosed with anastomotic recurrent rectal cancer after 14 months after surgery. The pelvic MRI scan showed invasion of the prostate and seminal vesicles, so NACRT was performed. Tumors were found to have decreased in size, although there was still some residual invasion of the prostate and seminal vesicle. Laparoscopic total pelvic exenteration (Lap-TPE), and combined excision of the anal elevator muscle and bladder were performed. Preoperative diagnosis was ycT4b, N0, M0, ycStage Ⅱ, and pathological diagnosis was pT4b (prostate and seminal vesicles), INF b, Ly2, v2, Pn1b, pPM0, pDM0, pRM0, and pN0. Laparoscopic surgery allowed to operate safely, with minimal blood loss and a good field of vision. After postoperative adjuvant chemotherapy, lung and liver metastasis appeared after 6 months after surgery, but there was no local recurrence. The patient is treated with chemotherapy, and the metastases are under control. The patient is survive 17 months after Lap-TPE.

A 60-year-old man underwent thoracoscopic subtotal esophagectomy and posterior mediastinal gastric tube reconstruction after neoadjuvant chemotherapy. One year and 8 months postoperatively, recurrence was observed in the abdominal lymph nodes around the celiac artery and abdominal aorta. Chemoradiotherapy was initiated, followed by chemotherapy. Two months after the completion of chemoradiotherapy, the patient developed epigastric pain and anorexia because of the necrotic lymph node penetrating the gastric tube with cavity formation. Upper gastrointestinal endoscopy revealed a 25- mm-sized ulcer with central necrotic slough on the posterior wall of the stomach. Abdominal symptoms alleviated after conservative treatment with fasting and administration of antibiotics, and the inflammatory reaction improved. Oral nutritional supplements were started on hospitalization day 7, and abdominal symptoms or inflammatory reactions did not recur after resuming diet. The patient was discharged on hospitalization day 39 when the general condition stabilized. Subsequently, chemotherapy was restarted, and no regrowth of metastatic lesions was observed on endoscopy or CT examination 4 months later. Three years and 8 months after the recurrence, the recurrent disease has been controlled.

We investigated the initial stages of head development using a new method to randomly label chicken epiblast cells with enhanced green fluorescent protein, and tracking the labeled cells. This analysis was combined with grafting mCherry-expressing quail nodes, or node-derived anterior mesendoderm (AME). These live imagings provided a new conception of the cellular mechanisms regulating brain and head ectoderm development. Virtually all anterior epiblast cells are bipotent for the development into the brain or head ectoderm. Their fate depends on the positioning after converging to the AME. When two AME tissues exist following the ectopic node graft, the epiblast cells converge to the two AME positions and develop into two brain tissues. The anterior epiblast cells bear gross regionalities that already correspond to the forebrain, midbrain, and hindbrain axial levels shortly after the node is formed. Therefore, brain portions that develop with the graft-derived AME are dependent on graft positioning.

Cancer immunotherapy, including vaccination, is considered a major scientific and medical breakthrough. However, cancer immunotherapy does not result in durable objective responses against colorectal cancer (CRC). To improve the efficacy of immunotherapy, the present study investigated several biomarkers for selecting patients who were expected to respond well to immunotherapy. Firstly, a comprehensive proteomic analysis was performed using tumor tissue lysates from patients enrolled in a phase II study, in which five human leukocyte antigen (HLA)-A*24:02-restricted peptides were administered. Sialic acid-binding immunoglobulin type lectin (Siglec)-7 was identified as a potential predictive biomarker. Subsequently, this biomarker was validated using western blot analysis, and immunofluorescence using tissue samples from the patients enrolled in the phase II study. The expression levels of Siglec-7 detected by immunofluorescence were quantified and their association with overall survival (OS) in patients treated with the peptide vaccine was examined. Furthermore, considering the important role of tumor-infiltrating lymphocytes (TILs) for CRC prognosis, the densities of CD3+, CD4+, CD8+ and forkhead box P3 (FOXP3)+ T cells in CRC tissues were examined and compared with Siglec-7 expression. The mean expression levels of Siglec-7 were significantly higher in patients with poor prognosis, with an OS of ≤2 years, as shown in comprehensive proteomic analysis (P=0.016) and western blot analysis (P=0.025). Immunofluorescence analysis demonstrated that Siglec-7 was expressed in intratumoral macrophages. The OS in patients with high Siglec-7 expression was significantly shorter than in that in patients with low Siglec-7 expression (P=0.017) in the HLA-A*24:02-matched patients. However, this difference was not observed in the HLA-unmatched patients. There was no significant difference in OS between patients according to the numbers of TILs, nor significant correlation between TILs and Siglec-7 expression. In conclusion, Siglec-7 expression in macrophages in tumor tissue may be a novel predictive biomarker for the efficacy of immunotherapy against metastatic CRC.

A 68-year-old man presented to our hospital. An upper gastrointestinal tract endoscopy performed elsewhere revealed an elevated lesion with a circumferential esophageal cancer(identified as small cell carcinoma). Perthe treatment forsmall cell cancer and the standard treatment for esophageal neuroendocrine carcinoma, 7 courses of CBDCA(5mg/m2)plus ETP (100mg/m2)were administered. The lesion shrank and the lymph node swelling disappeared and the patient was deemed to be in partial remission. Nine months later, however, the primary tumor increased in size. A transthoracic subtotal esophagectomy( laparoscope-assisted), 2 area dissection, and gastric tube reconstruction(post-sternal)were performed at 2 years and 10 months afterdiagnosis.

Neoadjuvant chemoradiotherapy(NACRT)was administered at our hospital to 3 patients with lower advanced rectal cancer; NACRT resulted in pathological complete response(pCR). Case 1: A 65-year-old man was diagnosed with T4aN1M0, cStage Ⅲb disease; after chemoradiotherapy(CRT), the clinical stage improved to T4aN0M0, ycStage Ⅱb. Laparoscopic Hartmann's procedure and D3 lymph node dissection were performed 51 days after CRT. No recurrence was observed 31 months after surgery. Case 2: A 67-year-old man was diagnosed with T4aN2M0, cStage Ⅲb disease; after CRT, the clinical stage improved to T4aN1M0, ycStage Ⅲa. Laparoscopic abdominoperitoneal resection and D3 lymph node dissection were performed 57 days after CRT. No recurrence was observed 21 months after surgery. Case 3: An 83-year-old woman was diagnosed with T4aN2M0, cStage Ⅲb disease; after CRT, the clinical stage improved to T4aN0M0, ycStageⅡb. Laparoscopic abdominoperitoneal resection and D3 lymph node dissection were performed 64 days after CRT. No recurrence was observed 16 months after surgery. Here, we report 3 cases of lower advanced rectal cancer involving curative resection following CRT, and we provide a short literature review.

An 82-year-old man with Stage Ⅳ advanced gastric cancer and multiple liver metastases was referred to our hospital. Chemotherapy using S-1 was administered, resulting in withdrawal from the usual course because of an adverse event of grade 4 anorexia. GIS and EOB-MRI showed a prominent tumor reduction in both lesions; however, despite this, distal gastrectomy, D2 lymph node dissection, liver biopsy for S3 lesion, partial liver resection for S6 lesion, and cholecystectomy were performed to obtain a therapeutic diagnosis. Pathology revealed that the tumor cells remained in the main liver metastatic lesions. Therapeutic effect was assessed as Grade 2. Although weekly paclitaxel followed by reduced S-1 dosage was introduced after surgery, the recurrent mass was observed in the para-aortic region after 2 years. Subsequently, para-aortic lymph node dissection was performed because no new lesion was detected. More than 10 years have passed without any recurrence since the first surgery. As part of a multidisciplinary treatment for far advanced gastric cancer with multiple liver metastases (Stage Ⅳ), conversion surgery might be considered effective.

A 56-year-old woman diagnosed with type 2 gastric cancer and multiple lymph node metastases(T3N3M1[lym], cStage Ⅳ)was treated with chemotherapy using trastuzumab with S-1 plus cisplatin for 6 cycles. The primary lesion showed PR, and lymph node metastases disappeared after the chemotherapy. Because of adverse events, she was administered with 2 additional cycles of trastuzumab with S-1 plus cisplatin and 6 cycles of trastuzumab with capecitabine plus oxaliplatin. However, the primary lesion increased in size. Therefore, she underwent distal gastrectomy and D1+ lymphadenectomy with para-aortic lymph node sampling as a conversion surgery. The pathological diagnosis was T2N0M0, pStage ⅠB, and the primary cancer was Grade 1a owing to the chemotherapeutic effect. She survives without recurrence or postoperative adjuvant therapies 3 years after the surgery.

An 82-year-oldwoman previously underwent total gastrectomy for gastric cancer at the age of 75 years. After 7 years of follow-up, a colonoscopy was performedto investigate the cause of constipation, which revealedan irregularity in the rectal submucosa. A colonoscopy-guidedbiopsy showedpoorly differentiatedad enocarcinoma, andthe immunohistochemical staining pattern showedMUC2(-), MUC5AC(+), CDX2(+), andCA1 25(-). FDG-PET showedintense uptake only at the rectum. Thus, laparoscopic high anterior resection was performed. Pathological findings showed that poorly differentiated adenocarcinoma and signet-ring cell carcinoma hadd evelopedmainly in the submucosa. In comparison with the immunohistological features of the previous gastric cancer, the rectal tumor hadsimilar morphological characteristics. The definitive diagnosis was rectal metastasis from gastric cancer. She has remained recurrence-free in the 20 months since this operation.

A 71-year-oldman with voice hoarseness was referredto our hospital for further examination. He was diagnosedwith unresectable Stage Ⅳb esophageal cancer, with direct invasion to the aorta andtrachea andmultiple metastases to the lymph nodes, lungs, and adrenal gland. Because his performance status(PS)was deemedto be favorable, he receivedchemotherapy with docetaxel(DOC), cisplatin, and5 -FU(DCF therapy). After 2 cycles of DCF therapy, the primary lesion was scarred. No malignant lesions were detected in the biopsy performed. No distant metastases were identified on PET-CT. As a subsequent treatment, S-1 plus DOC therapy was administered. Finally, single S-1 administration was continued. The treatment periodwas 14 months. Treatment was concludedbecause a complete response(CR)was maintained. Three years after the conclusion of treatment, CR remains maintained. The overall survival in cases of unresectable advanced esophageal cancer is saidto be 3-10 months, but there are remarkable cases such as this one. If a goodPS is maintained, treatment shouldbe actively considered because CR is possible.

Response functions of a 60-μm thick neutron silicon sensor to 8-MeV neutrons were obtained experimentally and simulated using a Monte Carlo code. The simulation reproduced the experimental results well, however it was found that the discrepancy was due to insufficient treatment of energy deposition process of both alpha particles and 25Mg nuclei emitted simultaneously from the 28 Si(n,α)25Mg reaction. Here, experimental detection efficiencies were well simulated, within 14% difference for neutron energies of 1.1, 2.5, 5, 8, and 15 MeV. An optimized neutron detection efficiency curve of the neutron sensor by weighting high energy contribution was in good agreement with an ambient-dose-equivalent curve, within a factor of 2 at neutron energies from 2.5 to 100 MeV.

Cancer stem-like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P-CSLCs). A P-CSLC-enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by 2-D electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P-CSLCs compared to parental cells. Flow cytometry analysis indicated that CRT was mostly localized to the surface of P-CSLCs and did not correlate with the levels of CD44v9, another P-CSLC biomarker. Furthermore, the side population in the CRThigh /CD44v9low population was much higher than that in the CRTlow /CD44v9high population. Calreticulin expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients' clinicopathological features and disease outcomes in the Cox proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and postoperative therapy. Our results suggest that CRT can serve as a biomarker of P-CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be considered as a therapeutic target for cancer immunotherapy.

The present study used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to compare survival benefits among 112 patients with resectable, stage II–IV esophageal squamous cell carcinoma (SCC) treated between 1996 and 2016 with neoadjuvant chemoradiotherapy (NAC) plus surgery (Group A, n=55) or with surgery alone (Group B, n=57). Their propensity scores (PS) were calculated using a multivariable logistic regression model in which age, sex, cancer site, primary tumor length, cTNM stage, lymph node metastasis and depth of tumor invasion were the independent variables, and used to match Groups A and B according to the IPTW and matching method. After IPTW and PSM, univariate analysis was used to assess overall survival (OS) and disease-free survival (DFS), followed by Cox proportional hazard models for OS using IPTW between the two groups and the subgroups. After PSM, 5-year OS and DFS were significantly higher in Group A (OS: 65.2%, DFS: 65.2%) compared with Group B (OS: 31.2%, DFS: 20.87%). Similarly, after IPTW, OS and DFS were significantly higher in Group A compared with Group B patients. Five-year OS was 73.18% for Group A and 37.69% for Group B (hazard ratio: 0.2899, 95% confidence interval: 0.1167–0.7205). To conclude, treatment was more effective in Group A patients with clinical stage II, N0 and T3 disease involving the mid-esophagus. It was concluded that for patients with esophageal SCC, NAC plus esophagectomy exhibited improved survival compared with surgery alone, as demonstrated by use of IPTW and PSM methods.

We revisit the sunspot drawings made by the Japanese astronomer Kunitomo Toubei during 1835-1836 and recount the sunspot group number for each image. There are two series of drawings, preliminary (P, containing 17 days with observations) and summary (S, covering 156 days with observations), all made using brush and ink. S is a compilation of drawings for the period from February 1835, to March 1836. Presently, the P drawings are available only for one month, September 1835; those of other periods have presumably been lost. Another drawing (I) lets us recover the raw group count (RGC) for 25 September 1836, on which the RGC has not been registered in the existing catalogs. We also revise the RGCs from P and S using the Zurich classification and determine that Kunitomo's results tend to yield smaller RGCs than those of other contemporary observers. In addition, we find that Kunitomo's RGCs and spot areas have a correlation (0.71) that is not very different from the contemporary observer Schwabe (0.82). Although Kunitomo's spot areas are much larger than those determined by Schwabe due to skill and instrument limitations, Kunitomo at least captured the growing trend of the spot activity in the early phase of the Solar Cycle 8. We also determine the solar rotation axis to estimate the accurate position (latitude and longitude) of the sunspot groups in Kunitomo's drawings., Comment: Main text 22 pages, reference 6 pages, 2 tables, and 12 figures. Figures with the original sunspot drawings are available only in the record version

Cancer stem cells (CSCs) have been studied for their self-renewal capacity and pluripotency, as well as their resistance to anticancer therapy and their ability to metastasize to distant organs. CSCs are difficult to study because their population is quite low in tumor specimens. To overcome this problem, we established a culture method to induce a pancreatic cancer stem-like cell (P-CSLC)-enriched population from human pancreatic cancer cell lines. Human pancreatic cancer cell lines established at our department were cultured in CSC-inducing media containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), neural cell survivor factor-1 (NSF-1), and N-acetylcysteine. Sphere cells were obtained and then transferred to a laminin-coated dish and cultured for approximately two months. The surface markers, gene expression, aldehyde dehydrogenase (ALDH) activity, cell cycle, and tumorigenicity of these induced cells were examined for their stem cell-like characteristics. The population of these induced cells expanded within a few months. The ratio of CD24high, CD44high, epithelial specific antigen (ESA) high, and CD44variant (CD44v) high cells in the induced cells was greatly enriched. The induced cells stayed in the G0/G1 phase and demonstrated mesenchymal and stemness properties. The induced cells had high tumorigenic potential. Thus, we established a culture method to induce a P-CSLC-enriched population from human pancreatic cancer cell lines. The CSLC population was enriched approximately 100-fold with this method. Our culture method may contribute to the precise analysis of CSCs and thus support the establishment of CSC-targeting therapy.

Background In the tumor microenvironment, factors inhibiting the targeting of cancer cells by activated T cells have recently been noted. B7-H3 belongs to the B7 superfamily of immune regulatory ligands and plays an important role in the adaptive immune response of co-inhibitory/stimulatory factors in regulating T cells. However, the degree to which B7-H3 directly affects tumor immune evasion mechanisms remains unclear, particularly in patients with breast cancer. Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The present study demonstrated that expression of B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment independently affected prognosis in breast cancer patients. Methods We immunohistochemically investigated the presence of B7-H3 and forkhead box P3 (Foxp3)-positive Tregs in pathological specimens from 90 patients with breast cancer. Results Positive B7-H3 expression was associated with shorter recurrence-free survival (RFS) (p = 0.014). A higher percentage of Foxp3-positive cells also correlated with shorter RFS (p = 0.039). Multivariate analysis showed B7-H3 as an independent factor on RFS. Foxp3 expression in tumor-infiltrating lymphocytes (TILs) correlated significantly with larger tumor size (>2 cm), expression of human epidermal growth factor receptor 2 (HER2), and higher nuclear grade (p = 0.003, p

1National Institute for Fusion Science, Toki 509-5292, Japan 2Sandia National Laboratories, Albuquerque, NM 87123-1129, USA 3Shimane University, Matsue 690-8504, Japan 4University of Californian, San Diego, CA 92093-0417, USA 5Kyushu University, Fukuoka 812-8581, Japan 6Shizuoka University, Shizuoka 422-8529, Japan 7Department of Materials Science and Engineering, University of Tennessee, Knoxville, USA 8Institute of Advanced Energy, Kyoto University, Kyoto 611-0011, Japan 9Pacific Northwest National Laboratory, Richland, WA 99352, USA 10Institute of Laser Engineering, Osaka University, Suita 5650871, Japan

'Candidatus Mycoplasma haemobos', sometimes causative of bovine infectious anemia at various extents, has been demonstrated throughout the world. Here, we show two distinct types of 'Ca. M. haemobos' are distributed among cattle in Japan, by examining the primary and secondary structures of the 16S-23S rRNA intergenic spacer region that has been shown to be a stable genetic marker for mycoplasma species. Our results may explain differences in severity of anemic condition as well as provide a genetic marker for an epidemiological study of bovine hemoplasma infections.

The prevalence of hemotropic mycoplasmas in wild rodents is largely unknown. Here, we report the presence of hemoplasmas in blood samples collected from brown sewer rats (Rattus norvegicus) trapped during rodent control around an animal hospital in Morioka, Japan. We examined nine rats using real-time PCR and end-point PCR, and found one rat (11.1%) that was positive for a hemoplasma infection. The 16S rRNA gene and 16S to 23S rRNA intergenic spacer region of the hemoplasma detected in a wild-caught rat were amplified using PCR. The nucleotide sequences of the PCR products were further determined and compared to those of other hemoplasmas. Our examinations revealed the presence of a hemoplasma that has not previously been described in rodents. The pathogenic traits of this hemoplasma remain unexplored.

The intergenic spacer region between the 16S and 23S rRNA genes of mycoplasmas has been used for a genetic marker for identification of the species. Here we show the intergenic spacer regions of two hemotropic mycoplasmas, Mycoplasma haemofelis and ` Candidatus Mycoplasma haemobos (synonym: `C. M. haemobovis')' are also useful for classification of this particular group of mycoplasms. The spacer region of M. haemofelis and `C. M. haemobos' consisted of 209 and 210 base pairs, respectively, and both lacked the spacer tRNA genes. Phylogenetic analysis suggested a monophyletic relationship among hemoplasmas and M. fastidiosum. A hypothetical secondary structure predicted in the spacer regions tentatively assigned the boxA and boxB motifs peculiar to the members of the genus Mycoplasma. M. haemofelis and `C. M. haemobos' possessed a stem-loop structure in common, despite the presence of a palindromic nucleotide substitution in the stem region.

Although swarmer morphotypes of Proteus mirabilis have long been considered to result from surfaced-induced differentiation, the present findings show that, in broth medium containing urea, acidic conditions transform some swimmer cells into elongated swarmer cells. This study has also demonstrates that P. mirabilis cells grown in acidic broth medium containing urea enhance virulence factors such as flagella production and cytotoxicity to human bladder carcinoma cell line T24, though no significant difference in urease activity under different pH conditions was found. Since there is little published data on the behavior of P. mirabilis at various hydrogen-ion concentrations, the present study may clarify aspects of cellular differentiation of P. mirabilis in patients at risk of struvite formation due to infection with urease-producing bacteria, as well as in some animals with acidic or alkaline urine.