ABSTRACT
BACKGROUND: Tick-borne diseases cause economically significant losses to animal production globally, and anaplasmosis and theileriosis are associated with the greatest losses. However, the spread of the relevant pathogens in flocks of domesticated animals in southern Egypt is little understood. Accordingly, in this study, we aimed to determine the prevalences of Anaplasma ovis, Theileria ovis, and Theileria lestoquardi in southern Egyptian sheep and goats through blood tests, and to make a molecular characterization of the A. ovis detected in sheep targeting a specific gene. RESULTS: We collected blood samples collected from 300 sheep and goats (n=150 /species) in Luxor Province in southern Egypt, and analyzed them for the presence of A. ovis, T. ovis and T. lestoquardi with screening by conventional and nested PCR targeting the msp4 and msp5, 18S rRNA, and merozoite surface protein genes. For A. ovis 140/300 samples (46.66%) were positive overall, with 90/150 (60%) and 50/150 (33.33%) positive samples in sheep and goats, respectively. Two major surface protein genes of A. ovis, msp4 and msp5, were sequenced using DNA extracted from sheep and goat blood samples, for phylogenetic analysis and genotyping. The msp4 gene sequence revealed no significant genetic diversity, to contrast to data on A. ovis strains from other countries. For T. lestoquardi, 8/150 (5.33%) samples were positive in sheep, but no samples were positive in goats (0%). For T. ovis, 32/150 (21.33%) samples were positive in sheep, but no samples were positive in goats (0%). Sequencing targeting the merozoite surface protein gene for T. lestoquardi and the small subunit ribosomal RNA gene for T. ovis revealed no significant genetic diversity in the study, another contrast to data on A. ovis strains from other countries. CONCLUSION: This study provides valuable data on phylogenetic and molecular classifications of A. ovis, T. ovis and T. lestoquardi found in southern Egyptian sheep and goats. It also represents the first report on detection and molecular characterization of T. lestoquardi in southern Egyptian sheep based on the specific merozoite surface protein gene, thus providing valuable data for molecular characterization of this pathogen in southern Egypt.
Subject(s)
Anaplasma ovis , Anaplasmosis , Goat Diseases , Goats , Sheep Diseases , Theileria , Theileriasis , Animals , Egypt/epidemiology , Theileria/genetics , Theileria/isolation & purification , Theileria/classification , Theileriasis/epidemiology , Sheep , Sheep Diseases/epidemiology , Sheep Diseases/microbiology , Sheep Diseases/parasitology , Goat Diseases/epidemiology , Goat Diseases/microbiology , Goat Diseases/parasitology , Anaplasmosis/epidemiology , Anaplasmosis/microbiology , Anaplasma ovis/genetics , Anaplasma ovis/isolation & purification , Prevalence , Phylogeny , Polymerase Chain Reaction/veterinaryABSTRACT
The case presented here is of a man in his 80s who was attending the Department of Neurology for Parkinson's disease. He had a fever and visited the emergency department. A CT scan revealed a 10 cm mass in the hepatic flexure that was suspected of invading the duodenum, as well as numerous enlarged lymph nodes around the mass. A colonoscopy revealed a semi-peripheral type 3 tumor, and a biopsy showed adenocarcinoma(tub1-tub2). A right hemicolectomy was performed, and the tumor was located in the hepatic flexure of the ascending colon and was found to be in a mass with lymph nodes and adhesions to the duodenum. Due to the invasiveness of the surgery and the decrease in ADL, the patient's postoperative course required prolonged hospitalization. He was transferred to the hospital at POD33 and discharged at POD64. Due to his old age, adjuvant chemotherapy was not administered, and he is still alive 1 year after surgery with no recurrence. Even though his hospital stay was prolonged due to his decreased ADL, he is now able to return home. Aggressive resection may provide good results even in elderly patients.
Subject(s)
Colonic Neoplasms , Parkinson Disease , Male , Humans , Aged , Colon, Ascending/surgery , Parkinson Disease/pathology , Colonic Neoplasms/surgery , Biopsy , Duodenum/pathologyABSTRACT
Granulocyte colony-stimulating factor(G-CSF)is known to cause bone pain, headache, and fatigue as side effects. We experienced 2 cases of aortitis caused by pegfilgrastim(PEG-G)administration. Case 1: A 50s woman with breast cancer started FEC therapy with PEG-G as neoadjuvant chemotherapy. She developed a fever in the 38â range, and chest CT showed wall thickening in the aortic arch. She was diagnosed with aortitis and administration of prednisolone was started, and the fever resolved and the general condition improved dramatically. Case 2: A 70s woman was started TC therapy with PEG-G as adjuvant chemotherapy after surgery. Fever, anorexia, and epigastralgia appeared. A CT scan of the abdomen revealed thickening of the abdominal aortic wall from the thoracoabdominal transition area to the renal artery bifurcation. She was diagnosed with PEG-G-induced aortitis, and administration of prednisolone was started. The fever resolved and the pain disappeared. Although the symptoms of G-CSF-induced aortitis are nonspecific, it is relatively easy to diagnose by CT and should be considered when a fever develops after G-CSF administration.
Subject(s)
Aortitis , Breast Neoplasms , Female , Humans , Aortitis/chemically induced , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Fever , Filgrastim/adverse effects , Granulocyte Colony-Stimulating Factor/therapeutic use , Pain/drug therapy , Polyethylene Glycols/adverse effects , Prednisolone/therapeutic use , Aged , Middle AgedABSTRACT
Severe fever with thrombocytopenia syndrome virus (SFTSV) is spreading rapidly in Asia. This virus is transmitted by the Asian longhorned tick (Haemaphysalis longicornis), which has parthenogenetically and sexually reproducing populations. Parthenogenetic populations were found in ≥15 provinces in China and strongly correlated with the distribution of severe fever with thrombocytopenia syndrome cases. However, distribution of these cases was poorly correlated with the distribution of populations of bisexual ticks. Phylogeographic analysis suggested that the parthenogenetic population spread much faster than bisexual population because colonization is independent of sexual reproduction. A higher proportion of parthenogenetic ticks was collected from migratory birds captured at an SFTSV-endemic area, implicating the contribution to the long-range movement of these ticks in China. The SFTSV susceptibility of parthenogenetic females was similar to that of bisexual females under laboratory conditions. These results suggest that parthenogenetic Asian longhorned ticks, probably transported by migratory birds, play a major role in the rapid spread of SFTSV.
Subject(s)
Bunyaviridae Infections , Ixodidae , Phlebovirus , Severe Fever with Thrombocytopenia Syndrome , Ticks , Animals , Bunyaviridae Infections/epidemiology , Female , Phlebovirus/genetics , PhylogenyABSTRACT
Xentuzumab is an insulin-like growth factor (IGF) ligand-neutralizing antibody. This phase 1 trial assessed xentuzumab in Japanese patients with solid tumors. Patients aged ≥20 y old with solid tumors that were refractory or not amenable to standard therapy were enrolled. Patients received xentuzumab intravenously at a starting dose of 750 mg/wk. Dose escalation used a 3 + 3 design with dose de-escalation. The primary endpoint was to determine the maximum tolerated dose (MTD) of xentuzumab. Safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity were also assessed. Fifteen patients received xentuzumab in the dose escalation part (750 mg/wk [n = 6]; 1000 mg/wk [n = 3]; 1400 mg/wk [n = 6]). There were no dose-limiting toxicities at any dose; the MTD of xentuzumab was not reached. Xentuzumab 1000 mg/wk was recommended as the relevant biological dose. Six further patients received xentuzumab 1000 mg/wk in an expansion cohort. Of 21 patients, 13 (61.9%) experienced a drug-related adverse event, most commonly fatigue (23.8%), neutropenia (19.0%), diarrhea, nausea, white blood cell count decrease, and muscle spasms (14.3% each). No relevant deviations from dose linearity of xentuzumab exposure were observed during dose escalation. Total IGF-1 and IGF-2 levels increased and bioactive IGF levels decreased from baseline to 24 h after the first infusion in cycle 1. Partial response was observed in 2 (9.5%) patients with desmoid-type fibromatosis. Disease control was achieved in 6 (28.6%) patients (median duration 42.4 mo). Xentuzumab monotherapy was well tolerated in Japanese patients and showed evidence of anti-tumor activity. This study was registered with www.clinicaltrials.gov (NCT02145741).
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , Insulin-Like Growth Factor II/immunology , Insulin-Like Growth Factor I/immunology , Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/pharmacokinetics , Antibodies, Neutralizing/immunology , Dose-Response Relationship, Drug , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor II/analysis , Japan , Male , Maximum Tolerated Dose , Middle Aged , Neoplasms/pathology , Treatment OutcomeABSTRACT
Recurrence is more common for breast cancer than other solid tumors. In the last 5 years, we experienced 8 cases that relapsed more than 10 years after initial treatment. All cases were hormone-sensitive and HER2-negative. The Ki-67 percentage score was less than 15% in 7 cases. The age range at recurrence was 56-93 years(mean, 74.6 years), and the time to recurrence was 10-14 years and 20 or more years in 6 and 2 cases(mean, 14.6 years), respectively. The triggers for diagnosis were subjective symptoms, follow-up, and examination for other diseases in 3, 3, and 2 cases, respectively. The recurrence sites included the axilla, pleura/lung, liver/lung, skin, and chest wall in 3, 2, 1, 1, and 1 case, respectively. Treatment included an aromatase inhibitor(AI)and AI plus CDK4/6 inhibitor in 5 and 3 cases, respectively. The post-recurrence treatment period was 6-31 months(mean, 21.6 months), with 4 cases of PR, 3 cases of SD, and 1 case of death from other disease. There were 3 cases of axillary recurrence and 1 case each of neuropathic pain, upper limb edema, and local pain; all were alleviated by the treatment. In 2 cases, the pleural effusion decreased without chest tube drainage. Hormone receptor- positive late-relapse cases are generally highly therapeutically sensitive with favorable prognosis. In many cases, AI alone was selected considering patient age, side effects, treatment costs, and other factors.
Subject(s)
Breast Neoplasms , Humans , Middle Aged , Aged , Aged, 80 and over , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Follow-Up Studies , Prognosis , Chemotherapy, Adjuvant , Hormones/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Receptor, ErbB-2ABSTRACT
A 60s woman was diagnosed with cecal cancer with multiple liver metastases(final pathology was T4aN1M1[H1])and underwent ileocecal resection and D3 dissection. She did not wish for postoperative chemotherapy and surgical treatment of liver metastases. One and a half years after surgery, she developed extremity edema of lower legs and hypoalbuminemia, and she gained 20 kg. Contrast-enhanced CT showed stenosis of the inferior vena cava due to liver metastases, which was markedly improved the symptoms by placement of an inferior vena cava stent. Inferior vena cava stent placement is a minimally invasive treatment and can be an option as it can be expected to improve quality of life in some cases.
Subject(s)
Liver Neoplasms , Vena Cava, Inferior , Constriction, Pathologic , Female , Humans , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Quality of Life , Stents , Treatment Outcome , Vena Cava, Inferior/pathology , Vena Cava, Inferior/surgeryABSTRACT
Tick infestations and tick-borne diseases are among the leading causes of economic losses in the cattle industry worldwide. Amitraz is one of the most commonly used chemical acaricides against the cattle tick Rhipicephalus (Boophilus) microplus. Resistance to amitraz has been reported in many countries but not in the Philippines. This study aimed to determine whether cattle ticks from provinces in northern and southern Luzon, Philippines, are resistant to amitraz. Engorged or nearly engorged female ticks were collected from 21 farms and allowed to lay eggs to produce larvae. Larval packet test (LPT) was performed using three concentrations of amitraz, as well as a negative control (diluent). Reverse-transcription polymerase chain reaction (RT-PCR) was also performed to amplify a fragment of the octopamine/tyramine receptor gene and was subjected to sequence analysis by multiple nucleotide and amino acid sequence alignments together with reference strain, amitraz-susceptible strain, and amitraz-resistant strain reported in other countries. LPT results suggest the absence of resistance in all of the tested populations. Interestingly, analysis of the octopamine/tyramine receptor amino acid sequence revealed four out of 14 larval pools having substitutions similar to that of the reported amitraz-resistant strains. Although no apparent resistance was observed in this study, prudent use of amitraz should be practiced as the development of resistance is still likely to occur in the future.
Subject(s)
Acaricides , Cattle Diseases , Rhipicephalus , Tick Infestations , Acaricides/pharmacology , Animals , Biological Assay , Cattle , Cattle Diseases/epidemiology , Female , Insecticide Resistance/genetics , Philippines , ToluidinesABSTRACT
Histopathological and genetic examinations were conducted on grayish-white solid hepatic nodules in 150 horses imported from Canada, in order to investigate larval Echinococcus multilocularis infection. Ten of the 150 horses (6.7%) were diagnosed with alveolar hydatid disease. The sequences of the mitochondrial cytochrome b genes obtained from all 10 polymerase chain reaction positive samples had 99 to 100% identity with the European haplotype E1 of E. multilocularis. Therefore, we concluded that the infections likely originated in Canada.
Relation entre les nodules hépatiques solides blanc-grisâtre trouvés chez des chevaux importés du Canada et l'infection larvaire à Echinococcus multilocularis . Des examens histopathologiques et génétiques ont été effectués sur des nodules hépatiques solides blanc-grisâtre observés chez 150 chevaux importés du Canada afin d'étudier l'infection larvaire à Echinococcus multilocularis. Dix des 150 chevaux (6,7 %) ont reçu un diagnostic de maladie hydatique alvéolaire. Les séquences des gènes mitochondriaux du cytochrome b obtenus à partir des 10 échantillons positifs par réaction d'amplification en chaîne par la polymérase ont montré une identité de 99 à 100 % avec l'haplotype européen E1 d'E. multilocularis. L'haplotype d'E. multilocularis obtenu à partir de cette étude suggère que les infections sont probablement originaires du Canada.(Traduit par Dr Serge Messier).
Subject(s)
Echinococcosis, Hepatic , Echinococcosis , Echinococcus multilocularis , Horse Diseases , Animals , Canada , Echinococcosis/veterinary , Echinococcosis, Hepatic/veterinary , Echinococcus multilocularis/genetics , Horses , LarvaABSTRACT
A man in his 70s was referred to our hospital for the examination of an abdominal tumor detected incidentally. The tumor was resected with a preoperative diagnosis of gastric submucosal tumor. As a result of the histopathological examination, dedifferentiated liposarcoma was diagnosed. The tumor recurred 2 months after the operation, and resection was attempted again. However, the intraoperative findings showed multiple metastatic lesions, and radical resection was considered impossible. Chemotherapy was therefore administered with doxorubicin monotherapy and eribulin, but the tumor rapidly increased, and the patient ultimately died 8 months after the initial operation. Dedifferentiated liposarcoma is a histologic type with a poor prognosis among liposarcoma. Resection is the standard treatment, but it frequently develops in the retroperitoneum, and it is often found in an advanced state due to the lack of subjective symptoms compared to lesions of the extremities. In addition, its tendency to infiltrate into the surrounding area and to metastasize are also factors that make radical resection difficult. We herein report a case of dedifferentiated liposarcoma that was detected asymptomatically but had a rapid outcome.
Subject(s)
Liposarcoma , Neoplasm Recurrence, Local , Abdomen , Humans , Liposarcoma/drug therapy , Liposarcoma/surgery , Male , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/surgeryABSTRACT
Here, we report 2 cases of locally advanced breast cancer with uncontrollable bleeding treated with mastectomy followed by skin transplantation. The operation restored the QOL and enabled chemotherapy in postoperative periods. Case 1: A woman in her 70s was brought by an ambulance because of heart failure symptoms. She had a huge breast tumor on her left chest wall that bled repeatedly, necessitating frequent blood transfusions. An operation was performed, and chemotherapy was provided until she died of brain metastasis 1 year and 8 months after surgery. Case 2: A woman in her 70s was urgently hospitalized with a lumbar vertebrae bone fracture. She had a huge breast tumor on her right chest wall that bled repeatedly. Blood examination revealed severe anemia. An operation was performed, and chemotherapy was introduced sequentially. She is alive with a good status 2 years and 1 month after surgery.
Subject(s)
Breast Neoplasms , Thoracic Wall , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Female , Humans , Mastectomy , Quality of Life , Skin Transplantation , Thoracic Wall/surgeryABSTRACT
A 54-year-old man underwent distal gastrectomy with D2 lymph node dissection in our institution in March 2017 due to the presence of advanced gastric cancer. The pathological diagnosis was signet ring, poorly differentiated, and moderate differentiated adenocarcinoma, which was pT4aN3aM0, pStage â ¢c and HER2-negative. After surgery, he received adjuvant chemotherapy with S-1, however, he was diagnosed with dissemination and lymph node recurrence in June. Tumor marker, CEA level decreased after the introduction of the next treatment(capecitabine plus cisplatin), however the tumor marker level rose again in September, and the chemotherapy regimen was changed to weekly paclitaxel(PTX). Furthermore, ramucirumab was added to the weekly PTX regime in January 2018, as the tumor marker level rose again. One week after the last ramucirumab administration he visited our hospital with abdominal pain, and emergency surgery was performed after the diagnosis of a gastrointestinal perforation using CT. The surgery revealed dirty fluid and countless dissemination nodes throughout the abdominal cavity, and a small intestinal perforation on a white dissemination node was identified 70 cm proximal to the end of the ileum. We performed small bowel segmental resection and functional end-to-end anastomosis. No complications were observed, and an oral diet was able to be started after surgery; however, he was introduced to the best supportive care(BSC)as his general condition gradually deteriorated.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Paclitaxel/adverse effects , Stomach Neoplasms , Gastrectomy , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , RamucirumabABSTRACT
A 60s man was diagnosed with unresectable advanced rectal cancer with synchronous solitary liver metastasis. Chemotherapy was administered and the primary tumor shrank immediately. However, he still demonstrated dorsal extension; therefore, chemotherapy was continued for approximately 1 year. After long-term chemotherapy, the primary tumor was deemed to be resectable because the dorsal extension had decreased. We achieved curative resection by performing a primary tumor and liver resection and he has shown no recurrence without adjuvant chemotherapy. Although the primary tumor was initially diagnosed as unresectable, it is important to consider the potential for curative resection after long-term chemotherapy.
Subject(s)
Liver Neoplasms , Rectal Neoplasms , Hepatectomy , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Male , Neoplasm Recurrence, Local , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , RectumABSTRACT
Ticks are key vectors of some important diseases of humans and animals. Although they are carriers of disease agents, the viability and development of ticks are not harmed by the infectious agents due to their innate immunity. Antimicrobial peptides directly protect hosts against pathogenic agents such as viruses, bacteria, and parasites. Among the identified and characterized antimicrobial peptides, defensins have been considerably well studied. Defensins are commonly found among fungi, plants, invertebrates, and vertebrates. The sequence of the tick hemolymph defensin (HEdefensin) gene from the hard tick Haemaphysalis longicornis was analyzed after identification and cloning from a cDNA library. HEdefensin has a predicted molecular mass of 8.15â¯kDa including signal peptides and a theoretical isoelectric point of 9.48. Six cysteine residues were also identified in the amino acids. The synthetic HEdefensin peptide only showed antibacterial activity against Gram-positive bacteria such as Micrococcus luteus. A fluorescence propidium iodide exclusion assay also showed that HEdefensin increased the membrane permeability of M. luteus. Additionally, an indirect fluorescent antibody test showed that HEdefensin binds to M. luteus. These results suggested that HEdefensin strongly affects the innate immunity of ticks against Gram-positive bacteria.
Subject(s)
Arthropod Proteins/immunology , Defensins/immunology , Hemolymph/immunology , Ixodidae/immunology , Animals , Gram-Positive Bacterial Infections/veterinary , Immunity, Innate/immunology , Micrococcus luteus/immunologyABSTRACT
Hydrogen peroxide (H2O2) and hydroxyl radicals (HO·) are generated through partial reduction of oxygen. The HO· are the most reactive and have a shorter half-life than H2O2, they are produced from comparatively stable H2O2 through Fenton reaction. Although controlling HO· is important and biologically advantageous for organisms, it may be difficult. Ticks are obligate hematophagous arthropods that need blood feeding for development. Ticks feed on vertebrate blood containing high levels of iron. Ticks also concentrate iron-containing host blood, leading to high levels of iron in ticks. Host-derived iron may react with oxygen in the tick body, resulting in high concentrations of H2O2. On the other hand, ticks have antioxidant enzymes, such as peroxiredoxins (Prxs), to scavenge H2O2. Gene silencing of Prxs in ticks affects their blood feeding, oviposition, and H2O2 concentration. Therefore, Prxs could play important roles in ticks' blood feeding and oviposition through the regulation of the H2O2 concentration. This review discusses the current knowledge of Prxs in hard ticks. Tick Prxs are also multifunctional molecules related to antioxidants and immunity like other organisms. In addition, tick Prxs play a role in regulating the host immune response for ticks' survival in the host body. Tick Prx also can induce Th2 immune response in the host. Thus, this review would contribute to the further understanding of the tick's antioxidant responses during blood feeding and the search for a candidate target for tick control.
Subject(s)
Peroxiredoxins/physiology , Ticks/physiology , Animals , Antioxidants , Feeding Behavior , Peroxiredoxins/immunology , Ticks/immunologyABSTRACT
Ticks require blood feeding on vertebrate animals throughout their life cycle, and also concentrate the iron-containing blood, resulting in a high concentration of hydrogen peroxide (H2O2). High concentrations of H2O2 are harmful to organisms, due to their serious damage of macromolecules. Ticks have antioxidant enzymes, such as peroxiredoxins (Prxs), that scavenge H2O2. Prxs may have important roles in regulating the H2O2 concentration in ticks during blood feeding and oviposition. Moreover, Prxs are considered potential vaccine candidates in other parasites, such as Leishmania and Fasciola. In the present study, the efficacy of a tick Prx (HlPrx2) as a vaccine candidate antigen was evaluated. First, recombinant HlPrx2 (rHlPrx2) was expressed in Escherichia coli, and then, its purity and endotoxin levels were confirmed prior to administration. The rHlPrx2 proteins were of high purity with acceptably low endotoxin levels. Second, the ability of rHlPrx2 administration to stimulate mouse immunity was evaluated. The rHlPrx2 protein, with or without an adjuvant, could stimulate immunity in mice, especially the IgG1 of Th2 immune response. Using Western blot analysis, we also observed whether rHlPrx2-immunized mice sera could recognize native HlPrx2 protein in crude tick midgut proteins. Western blot analysis demonstrated that rHlPrx2-administrated mouse sera could detect the native HlPrx2. Finally, the effects of rHlPrx2 immunization in mice were studied using nymphal ticks. Although the challenged ticks were not affected by rHlPrx2 immunization, rHlPrx2 still might be considered as a vaccine candidate against ticks because of its high immunogenicity.
Subject(s)
Arthropod Proteins/immunology , Immunologic Factors/immunology , Ixodidae/immunology , Peroxiredoxins/immunology , Tick Infestations/veterinary , Vaccines/immunology , Animals , Female , Mice , Mice, Inbred BALB C , Tick Infestations/prevention & controlABSTRACT
A 60s man was diagnosed as having unresectable advanced rectal cancer with swelling of the para-aortic lymph nodes. Chemotherapy was administered, and the primary tumor immediately shrank. He still had para-aortic lymph node swelling; therefore, chemotherapy was continued for approximately 2 years. After long-term chemotherapy, we diagnosed his tumor as resectable because the para-aortic lymph node swelling had shrunk. We achieved curative resection, and he has shown no recurrence without adjuvant chemotherapy. Although chemotherapy is the main treatment for unresectable advanced colorectalcancer, it is important to consider curative resection, as in this case with long-term chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Rectal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Neoplasm Recurrence, Local , Rectal Neoplasms/drug therapy , Rectal Neoplasms/surgeryABSTRACT
Spatial organization of different epigenomic marks was used to infer functions of the epigenome. It remains unclear what can be learned from the temporal changes of the epigenome. Here, we developed a probabilistic model to cluster genomic sequences based on the similarity of temporal changes of multiple epigenomic marks during a cellular differentiation process. We differentiated mouse embryonic stem (ES) cells into mesendoderm cells. At three time points during this differentiation process, we used high-throughput sequencing to measure seven histone modifications and variants--H3K4me1/2/3, H3K27ac, H3K27me3, H3K36me3, and H2A.Z; two DNA modifications--5-mC and 5-hmC; and transcribed mRNAs and noncoding RNAs (ncRNAs). Genomic sequences were clustered based on the spatiotemporal epigenomic information. These clusters not only clearly distinguished gene bodies, promoters, and enhancers, but also were predictive of bidirectional promoters, miRNA promoters, and piRNAs. This suggests specific epigenomic patterns exist on piRNA genes much earlier than germ cell development. Temporal changes of H3K4me2, unmethylated CpG, and H2A.Z were predictive of 5-hmC changes, suggesting unmethylated CpG and H3K4me2 as potential upstream signals guiding TETs to specific sequences. Several rules on combinatorial epigenomic changes and their effects on mRNA expression and ncRNA expression were derived, including a simple rule governing the relationship between 5-hmC and gene expression levels. A Sox17 enhancer containing a FOXA2 binding site and a Foxa2 enhancer containing a SOX17 binding site were identified, suggesting a positive feedback loop between the two mesendoderm transcription factors. These data illustrate the power of using epigenome dynamics to investigate regulatory functions.
Subject(s)
Cluster Analysis , Epigenesis, Genetic , Epigenomics , Gene Expression Regulation , Models, Molecular , Animals , Cell Differentiation/genetics , DNA Methylation , Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , Genome , Histones/chemistry , Histones/metabolism , Mice , Promoter Regions, Genetic , Transcription, Genetic , TranscriptomeABSTRACT
PURPOSE: To evaluate the incidence of major adverse cardiac events (MACE) and long-term surgical outcomes after gastrectomy for gastric cancer using the revised cardiac risk index (RCRI), which is based on preoperative insulin use, serum creatinine >2.0 mg/dL, and history of ischemic or congestive heart failure or cerebrovascular disease. METHODS: We allocated 1000 patients who underwent elective gastrectomy to three groups with ≥3 (group A, n = 32), 2 (group B, n = 142), or 1 (group C, n = 826) of these factors and compared surgical complications and prognoses. RESULTS: Groups A and B had older patients than group C. Group B had more male patients than groups A and C. Tumor staging and gastrectomy type were similar among all groups. D1 lymph node dissection was more frequent in group A than in groups B or C. The incidence of MACE in groups A, B, and C was 25.0, 9.9, and 1.1 %, respectively. RCRI was associated with MACE. Furthermore, the incidence of pneumonia and in-hospital mortality was associated with RCRI risk factors. However, the incidence of anastomotic leakage, intra-abdominal abscess, wound infection, and pancreas-related infection were similar among the groups. The 5-year overall survival rates of the three groups were 44.3, 65.2, and 80.8 %, which were significantly different. CONCLUSIONS: Patients with RCRI factors have an increased risk of MACE, pneumonia, and higher mortality after gastrectomy; thus, careful patient selection and meticulous perioperative care are crucial for successful gastrectomy.
Subject(s)
Adenocarcinoma/surgery , Gastrectomy/adverse effects , Heart Failure/diagnosis , Postoperative Complications , Stomach Neoplasms/surgery , Adenocarcinoma/secondary , Aged , Female , Follow-Up Studies , Heart Failure/etiology , Humans , Lymph Node Excision/adverse effects , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Preoperative Care , Prognosis , Retrospective Studies , Risk Assessment , Stomach Neoplasms/pathology , Survival RateABSTRACT
BACKGROUND: The aim of this study was to investigate the impact of being underweight on the long-term outcomes of gastric cancer patients. METHODS: This study reviewed the medical records of 638 patients with gastric cancer who underwent gastrectomy between January 2003 and December 2011. The patients were divided into three groups according to the WHO classification: underweight (BMI <18.5 kg/m(2)), normal weight (BMI ≥18.5 and <25 kg/m(2)), and overweight (BMI ≥25 kg/m(2)). A multivariate analysis was performed to identify prognostic factors. RESULTS: The mean BMI immediately before surgery was 22.5 kg/m(2) (standard deviation, 3.3 kg/m(2)). According to the BMI subgroup, 73 patients (11.4 %) were underweight, 431 patients (67.6 %) were of normal weight, and 134 patients (21 %) were overweight. The 5-year overall survival (OS) rate was 66.6 % in the underweight patients, 81.3 % in the normal weight patients, and 79.9 % in the overweight patients (P = 0.001). The OS rate was significantly lower in the underweight patients than in the normal weight and overweight patients among those with stage I disease, and it was also lower than in the normal weight patients among those with stage II and III disease. In the multivariate analysis, being underweight was found to be an independent predictor of OS, but it was not an independent predictor among patients with stage II and III disease. CONCLUSIONS: Being underweight is a simple and reliable predictor of a worse long-term outcome among gastric cancer patients. Being underweight is considered to be associated with a higher risk of non-cancer death.