Gut microbiota and fecal metabolites in sustained unresponsiveness by oral immunotherapy in school-age children with cow's milk allergy.

BACKGROUND: Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA. METHODS: We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules. RESULTS: During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the Bifidobacterium-dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kUA/L increments, 0.67 and 0.66; 95%CI, 0.41-0.93 and 0.42-0.90; Bifidobacterium-dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10-2.03), and these associations were observed until the end of OIT. CONCLUSIONS: In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT.

[Sixteen Cases of Appendiceal Mucinous Neoplasm].

Appendiceal mucinous neoplasm is a relatively rare disease. It is classified as mucinous adenocarcinoma(MACA)and low- grade appendiceal mucinous neoplasm(LAMN). We retrospectively evaluated 16 cases of appendiceal mucinous neoplasm (LAMN: 13 cases, MACA: 3 cases)that were surgically resected in our hospital between January 2010 and July 2021. There were 7 men and 9 women, with a median age of 61 years(27-85 years). The most common chief complaint was abdominal pain(12 patients), while 3 cases were incidental findings following medical checkups for other diseases and without a chief complaint. Colonoscopy was performed for 9 cases. Of these, 5 revealed abnormal findings. The preoperative diagnosis was appendicitis in 7 patients and appendiceal tumor in 8 patients. The surgical procedures were planned for 8 cases and performed as emergencies in 8 cases. The procedures included laparoscopic surgery(n=6)and laparotomy(n=10). The resection range included appendectomy(n=9), partial cecal resection(n=4), and ileocecal resection(n=3). Surgical margins were negative in all cases. Metastases were not observed in patients who underwent lymph node dissections (2 patients with MACA and 1 patient with LAMN). The median follow-up was 17 months(1-43 months). Recurrence including peritoneal pseudomyxoma was not detected in any of the patients.

Anti-Ascaris IgE as a Risk Factor for Asthma Symptoms among 5-Year-Old Children in Rural Bangladesh with Even Decreased Ascaris Infection Prevalence.

BACKGROUND: Epidemiological studies have indicated that anti-Ascaris IgE enhances asthma and allergies under specific conditions although the association between them is still controversial. The association of anti-Ascaris IgE with increased asthma symptoms among children from a general population with a mild to moderate Ascaris infection prevalence was investigated. METHODS: A total of 126 children aged 5 years with wheezing during the previous year and 110 children who did not have wheezing were selected randomly from the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Serum levels of total, anti-Ascaris, anti-Dermatophagoides pteronyssinus, and anti-cockroach IgEs were tested, and their risks for wheezing were analyzed. The wheezing children were then classified by hierarchical cluster analysis to investigate the contribution of anti-Ascaris IgE to wheezing. RESULTS: The anti-Ascaris IgE levels in wheezing and never-wheezing children were 1.07 and 0.65 UA/mL, and it contributed to 11% of wheezing in children. Anti-Ascaris IgE was significantly associated with wheezing (odds ratio [OR] per loge increment: 1.37 [95% CI: 1.01-1.87], p = 0.046). The ORs, which were adjusted for sex, parental asthma, pneumonia history, helminth infections, Haemophilus influenzae type B combination vaccination, antibiotic use during infancy, and total and specific IgE levels, increased even when only children with more specific symptoms of asthma were included in the analysis. Namely, the ORs for wheezing with sleep disturbance, four or more attacks, and wheezing with speech difficulties during the previous 1 year were OR = 1.44/loge increment [95% CI: 1.01-2.07], OR = 1.90/loge increment [95% CI: 1.11-3.25], and OR = 1.78/loge increment [95% CI: 1.01-3.14], respectively. CONCLUSIONS: The anti-Ascaris IgE levels in wheezing and never-wheezing children in the current study significantly decreased concurrently with Ascaris infection prevalence compared with their corresponding values in 2001. The contribution of anti-Ascaris IgE to wheezing also dropped from 26% in 2001 to 11% in the current study. Despite significant decreases in the levels and the seroprevalence and its contribution to wheezing, anti-Ascaris IgE remained significantly associated with increased risk of wheezing. Anti-Ascaris IgE significantly increased the risk of wheezing in a general population with a mild to moderate Ascaris infection prevalence, suggesting robustness as a risk factor and a possible dose-response relationship.

[Case Report of an Elderly Patient with Interstitial Pneumonia Caused by the Administration of Trastuzumab plus Anastrozole for the Treatment of Inflammatory Breast Cancer].

An 83‒year‒old woman received trastuzumab plus anastrozole as first‒line chemotherapy for inflammatory breast cancer in her left breast. Following the treatment, the induration and redness in her breast gradually improved; however, 2 days after receiving the 5th course of chemotherapy, she developed dyspnea and was referred to the emergency room. Her SpO2 was 88%; her KL‒6 level had increased to 2,613 U/mL; and a chest CT scan showed ground‒glass opacity in the bilateral lung fields, yielding a diagnosis of interstitial pneumonia requiring steroid pulse therapy. The dyspnea improved immediately after steroid administration, and the patient was discharged 20 days after hospitalization. Thereafter, the steroid dosage was gradually lowered to 5 mg/day. We discontinued steroid therapy after a chest CT confirmed the reduction of ground‒glass opacity. However, she was later readmitted for interstitial pneumonia for which she was readministered steroid pulse therapy. Trastuzumab‒induced interstitial pneumonia is rare, but we must be aware of the possibility that patients may develop severe pulmonary disorders or experience cardiotoxic effects.

Impact of Haemophilus influenzae type b combination vaccination on asthma symptoms and pneumonia in 5-year-old children in rural Bangladesh: a longitudinal study and comparison with a previous cross-sectional study.

BACKGROUND: Although the prevalence of bronchial asthma has been increasing worldwide since the 1970's, the prevalence among 5-year-old children was significantly lower in 2016 than in 2001 in rural Bangladesh. We aimed to determine whether the Haemophilus influenzae type b (Hib) combination vaccination (without booster) started in 2009 contributed to this decrease. METHODS: A case-control study was conducted among 1658 randomly selected 5-year-old children from Matlab, Bangladesh. Data on wheezing were collected using the International Study of Asthma and Allergies in Childhood questionnaire. The vaccination data were collected from the records of the Matlab Health and Demographic Surveillance System, while data on pneumonia were obtained from the clinical records of Matlab Hospital. Adjusted odds ratios (aORs) were calculated for the risk for wheezing. The reduction rate was calculated to determine the impact of the vaccination on pneumonia history between the present study and our previous study conducted in 2001 by using the following formula: (percentage of pneumonia cases in 2001 - percentage of pneumonia cases in 2016)/(percentage of pneumonia cases in 2001) times 100 (%). RESULTS: Hib combination vaccination was a protecting factor against wheezing (aOR: 0.50; p = 0.010), while pneumonia at 1, 2, 3-4 years of age were risk factors for wheezing (aOR: 2.86, 3.19, 2.86; p = 0.046, 0.030, 0.030, respectively). The history of pneumonia was significantly lower in the 2016 study participants than those in 2001 both in the overall cohort and the wheezing group (paired t-test: p = 0.012, p < 0.001, respectively). Whereas the history of pneumonia decreased when the children grew older in the 2001 overall cohort, it peaked at the age of 2 years in 2016 wheezing group. The reduction rate decreased when children grew older in both the overall cohort and the wheezing group, however, it decreased faster in the wheezing group. CONCLUSIONS: Hib combination vaccination was a protective factor against wheezing in 0-year-old children. However, the effects of vaccination might have attenuated at the ages of 1-4 years, because no booster dose was administered. The addition of a booster dose might further decrease the prevalence of asthma and wheezing.

Pancreaticoduodenectomy with malrotation following reoperation due to torsion of efferent loop: a case report.

BACKGROUND: Malrotation is a congenital anomaly during the development of the embryonic intestine. Although it is generally considered a pediatric surgical condition, it can have significant implications for adult surgery in terms of reconstruction. CASE PRESENTATION: The patient was an 85-year-old man with pancreatic cancer and intestinal malrotation. He underwent pancreaticoduodenectomy with modified Child's reconstruction. Because the ascending colon and efferent loop twisted easily, we fixed the ascending colon to the abdominal wall. Thereafter, right twist and stenosis of the efferent loop occurred. On the 22nd day after the initial surgery, detorsion and Braun anastomosis were performed for efferent loop fixation. Postoperative oral intake was good, and the patient was discharged from our hospital on the 24th day after the reoperation. CONCLUSIONS: This is a rare case of pancreaticoduodenectomy with malrotation following reoperation due to a complication after Child's reconstruction. In similar cases of intestinal malrotation, it is important to consider avoiding coaxial positioning of intestinal parts and an upper abdominal space while selecting a reconstruction method.

Molecular detection of enteric viruses in the stool samples of children without diarrhea in Bangladesh.

A number of molecular epidemiological studies reported the detection of enteric viruses in asymptomatic children. The role of these viruses in an asymptomatic infection remains unclear. This study investigated the enteric viruses in the stool samples collected from children without diarrhea. Stool samples were collected during June to October 2016, from 227 children who lived in Matlab, Bangladesh. Seventeen enteric viruses, including rotavirus A, B, and C (RVA, RVB, and RVC), norovirus GI (NoV GI), norovirus GII (NoV GII), sapovirus (SaV), adenovirus (AdV), human astrovirus (HAstV), Aichivirus (AiV), human parechovirus (HPeV), enterovirus (EV), human bocavirus (HBoV), Saffold virus (SAFV), human cosavirus (HCoSV), bufavirus (BufV), salivirus (SalV), and rosavirus (RoV), were investigated by RT-PCR method. One hundred and eighty-two (80.2%; 182/227) samples were positive for some of these viruses, and 19.8% (45/227) were negative. Among the positive samples, 46.7% (85/182) were a single infection, and 53.3% (97/182) were coinfection with multiple viruses. The HCoSV was the most prevalent virus (41.4%), followed by EV (32.2%), NoV GII (25.6%), HPeV (8.8%), RVA (6.2%), AdV (5.7%), AiV (5.3%), SAFV (4.4%), and SaV (2.6%). Each of NoV GI, HAstV, HBoV, and BufV was detected at 0.4%. However, RVB, RVC, SalV, and RoV were not detected in this study. Phylogenetic analysis showed that diverse HCoSV species and genotypes were circulating in Bangladesh, and four strains of species A are proposed to be new genotypes. The data indicated that non-diarrheal Bangladeshi children were asymptomatically infected with wide varieties of enteric viruses.

Classification of Wheezing Children in Rural Bangladesh by Intensity of Ascaris Infection, Total and Specific IgE Levels, History of Pneumonia, and Other Risk Factors.

Ascaris lumbricoides is the most common soil-transmitted helminth and infects 447 million people in impoverished areas worldwide. It causes serious morbidity including wheezing and influences various aspects of human immunity, such as type 2 innate lymphoid cells, regulatory T cell function, and acquired immunity. Thus, it is crucial to elucidate its influence on human immunity. We aimed to classify wheezing children based on their Ascaris infection intensity and other risk factors using hierarchical cluster analysis to determine the mechanisms of and the degree to which Ascaris contributes to childhood wheezing in rural Bangladesh. We analyzed relevant data collected in 2001. The participants included 219 5-year-old wheezing children who were randomly selected from 1705 children living in the Matlab Health and Demographic Surveillance area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Hierarchical cluster analysis was conducted using variables of history of pneumonia, total and specific immunoglobulin E levels, Ascaris infection intensity, and parental asthma. Three distinct wheezing groups were identified. Children in Cluster 1 (n = 50) had the highest titers of the total, anti-Ascaris, anti-Dermatophagoides pteronyssinus, and anticockroach IgEs and experienced the fewest episodes of pneumonia. Cluster 2 (n = 114), the largest group, experienced few episodes of pneumonia and had the lowest titers of the total, anti-Ascaris, anti-Dp, and anticockroach IgEs. Cluster 3 (n = 32) consisted of participants with the most episodes of pneumonia and lower titers of the total and specific IgEs. The extremely high prevalence of Ascaris infection found in Clusters 1-3 was 78%, 77%, and 72%, respectively. Childhood wheezing in rural Bangladesh could be divided into three groups, with 26% of wheezing attributable to anti-Ascaris IgE and 16% to history of pneumonia during early childhood, and 58% might have been due to Ascaris infection without elevated anti-Ascaris IgE.

[A Case of an Elderly Patient with Multiple Lung Metastases of Postoperative Pancreatic Cancer in Whom Lung Metastases Were Controlled by Biweekly Dose-Down Administration of Gemcitabine].

An 80-year-old woman was diagnosed with pancreatic head cancer, and pancreaticoduodenectomy was performed. Twelve months after the operation, chest CT scans showed the presence ofmultiple nodules in both the lungs. Because ofthe potential negative side effects of anti-cancer drugs, the patient underwent chemotherapy with dose-down biweekly adminis- tration ofgemcitabine (1,000mg/day/body≒750mg/m2. Chest CT examination every 2-3 months revealed no rapid increase in multiple tumors. Nineteen months after starting gemcitabine therapy, there was an elevation in tumor marker and a gradual increase in lung metastases. We performed combination chemotherapy with nab-paclitaxel. However, owing to side effects, only 2 courses of nab-paclitaxel were administered, and the therapy was switched to only gemcitabine administration. Later, respiratory distress accompanied by pleural effusion developed, and the patient died of the original disease 27 months after recurrence. Here, we report a case ofan elderly patient with multiple lung metastases ofpancreatic cancer in whom lung metastases were controlled by biweekly dose-down administration of gemcitabine.

A long-term survival case after resection of the pancreatic metastasis from lung cancer.

INTRODUCTION: Pancreatic metastasis from lung cancer is not an indication for surgical resection because patients with such a condition present with multiple-organ metastases. Therefore, the significance of resection in patients with pancreatic metastasis from lung cancer remains unclear. Here we report a case of a long-term survivor of pancreatic metastasis from lung cancer after pancreatectomy. CASE PRESENTATION: A 67-year-old woman presented with a pancreatic mass. She had undergone left lower lobectomy for stage IIIA lung adenocarcinoma 6 years prior to presentation. Following surgery, she received adjuvant treatment with gefitinib for 7 months. However, this treatment was discontinued due to its side effects. The patient received radiation therapy for mediastinal lymph node metastasis 2 years after resection and she became cancer-free. Six years after the initial pulmonary resection, the patient's tumor marker level increased, and abdominal computed tomography (CT) revealed a 20-mm tumor in the pancreatic tail. Positron emission tomography-CT revealed an abnormal uptake in the pancreatic tail. However, no other abnormal lesions were observed. The diagnosis was primary pancreatic cancer or metastasis from lung cancer. Distal pancreatectomy with lymph node dissection was performed, and the pathological diagnosis was metastasis from lung cancer. The patient survived for more than 5 years without recurrence but she died of acute renal failure after acquiring pneumonia. CONCLUSION: Surgical treatment should be considered for pancreatic metastasis from lung cancer if the disease is localized and the patient's condition is good. Additionally, combined therapy, including surgical resection, may be effective for repeated recurrence.

Concurrent decreases in the prevalence of wheezing and Ascaris infection among 5-year-old children in rural Bangladesh and their regulatory T cell immunity after the implementation of a national deworming program.

INTRODUCTION: Epidemiological research on the prevalence of asthma and helminthic infections in various countries has led to the hypothesis that helminthic infections protect against asthma by suppressing the host's immune response. This study was conducted to elucidate whether decreased Ascaris infection following a national deworming program was associated with increased recurrent wheezing among rural Bangladeshi children and to test their anti-inflammatory immunity. METHODS: This nested case-control study was conducted from December 2015 to October 2016 in the rural service area of the International Centre for Diarrhoeal Disease Research, Bangladesh. Of the 1800 5-year old children randomly selected for the study, informed consent was obtained from the guardians of 1658 children. Data were collected using a semistructured questionnaire adopted from the International Study of Asthma and Allergies in Childhood and blood samples for the analysis of regulatory T (Treg) cell immune responses and the balance between Th1 and Th2 immunity in Ascaris infections. RESULTS: A total of 145 children were found to have wheezing, yielding a prevalence rate of 8.7%, which was significantly lower than the rate found in 2001 (16.2%, P < .001); Ascaris infection also decreased from 2001 to 2016. The 127 wheezing children who agreed to participate further were compared to 114 randomly selected never-wheezing children. Wheezing had a significant positive association with antibiotic use, history of pneumonia, parents' history of asthma, and Ascaris infection; children with Ascaris infection were twice as likely to have wheezing (adjusted odds ratio = 2.31, P = .053). Flow cytometry found no significant differences in the rates of Th1, Th2, and CD4 + CD25 + CD127low cells by the wheezing group. CONCLUSIONS: Ascaris infection had a positive rather than a negative association with wheezing and the rates of wheezing and Ascaris infections both decreased from 2001 to 2016. These findings undermines the hypothesis that such infections provide protection against asthma.

[Usefulness of CT Colonography for a Patient with Three Synchronous Primary Descending Colon Cancers].

An 81-year-old woman presented with melena. Colonoscopy showed descending colon cancer, but the oral side of the tumor was excluded from observation because of easy bleeding related to the stenosis. CT colonography to evaluate the oral end of the intestine revealed 2 lesions in addition to the lesion observed on endoscopy. Before the surgery, the patient was suspected to have 3 synchronous primary descending colon cancers and underwent left hemicolectomy. Because CT colonography revealed synchronous multiple colon cancers in the patient, we performed surgery in one stage.

[A Case of Anastomotic Stage â Cecal Cancer Recurrence after Functional End-To-End Anastomosis].

An 83-year-old woman was referred to our hospital for cecal cancer, and ileocecal resection(D3 lymph node resection) with functional end-to-end anastomosis. Since the tumor was of histological Stage Ⅰ, no adjuvant chemotherapy was performed. One year and 9 months after the operation, an anastomotic recurrence was identified alongthe staple line using colonoscopy. We performed a resection of the anastomotic recurrence. At present, 6 months after the second operation, the patient remains in good health without evidence of recurrence. A few cases of anastomotic recurrence after surgery for Stage Ⅰcolon cancer have been reported in the literature available in Japanese. We report a rare case of an anastomotic recurrence of Stage Ⅰ cancer after functional end-to-end anastomosis.

[A Case of a One-Stage Resection and Anastomosis Procedure for a Descending Colon Cancer Ileus after Decompression with a Trans-Nasal Ileus Tube].

A 72-year-old man presented to our hospital with a chief complaint of constipation and hiccup. Computed tomography revealed a colonic obstruction due to descending colon cancer, and a transnasal ileus tube was inserted. On the 2nd day of hospitalization, we attempted transanal drainage, but it was difficult to cannulate. Abdominal findings and inflammatory response were normal; thus, the transanal drainage procedure was followed by only decompression with a transnasal ileus tube. On the 13th day of hospitalization, the tip of the ileus tube reached the vicinity of the occluded area. We performed a one-stage resection and anastomosis procedure. The patient was discharged from the hospital on the 16th postoperative day. Patients with left-sided colorectal cancer ileus are often immediately treated with colostomy when trans-anal decompression is difficult. We report a case of one-stage resection and anastomosis procedure for a descending colon cancer ileus after decompression with a transnasal ileus tube.

Desensitization to a whole egg by rush oral immunotherapy improves the quality of life of guardians: A multicenter, randomized, parallel-group, delayed-start design study.

BACKGROUND: Patients with food allergies and their families have a significantly reduced health-related quality of life (QOL). METHODS: We performed a multicenter, randomized, parallel-group, delayed-start design study to clarify the efficacy and safety of rush oral immunotherapy (rOIT) and its impact on the participants' daily life and their guardians (UMIN000003943). Forty-five participants were randomly divided into an early-start group and a late-start group. The early-start group received rOIT for 3 months, while the late-start group continued the egg elimination diet (control). In the next stage, both groups received OIT until all participants had finished 12 months of maintenance OIT. RESULTS: The ratio of the participants in whom an increase of the TD was achieved in the first stage was significantly higher in the early-start group (87.0%), than in the late-start group (22.7%). The QOL of the guardians in the early-start group significantly improved after the first stage (65.2%), in comparison to the late-start group (31.8%). During 12 months of rOIT, the serum ovomucoid-specific IgE levels, the percentage of CD203c+ basophils upon stimulation with egg white, and the wheal size to egg white were decreased, while the serum ovomucoid-specific IgG4 levels were increased. However, approximately 80% of the participants in the early-start group showed an allergic reaction during the first stage of the study, whereas none of the patients in the late-start group experienced an allergic reaction. CONCLUSIONS: rOIT induced desensitization to egg and thus improved the QOL of guardians; however, the participants experienced frequent allergic reactions due to the treatment.

Surgical outcome of laparoscopic hepatic resection for hepatocellular carcinoma: A matched case-control study with propensity score matching.

BACKGROUND: Although the number of reports on laparoscopic hepatic resection (LHR) has increased, studies of long-term outcomes regarding tumor recurrence and patient survival compared to the conventional open approach are limited. We evaluated the long-term survival and feasibility of LHR in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A retrospective analysis was performed on the clinical data of patients who underwent hepatic resection for primary HCC between August 2000 and December 2013. The patients were divided into the LHR or open hepatic resection (OHR) groups. To control for selection bias in the two groups, propensity score matching was used at a 1:1 ratio based on the following covariates: Child-Pugh grade, tumour size, tumour number and tumour location. Following propensity score matching, thirty patients were included in the LHR group and thirty were included in the OHR group. RESULTS: The respective disease-free survival rates at 1 year, 3 years and 5 years were 78.4%, 61.1% and 38.9%, respectively, for the LHR group, and 89.3%, 57.5% and 47.9%, respectively, for the OHR group (P = 0.89). Also, the overall survival rates at 1 year, 3 years and 5 years were 96.4%, 68.2% and 62.5%, respectively, for the LHR group and 100.0%, 95.8% and 72.3%, respectively, for the OHR group (P = 0.44). CONCLUSIONS: According to our study, using propensity score matching, LHR for HCC is safe, feasible and comparative, with good oncologic results.

[A Case of Intractable Pain Caused by Retroperitoneal Primary Unknown Cancer Recurrence That Was Improved by Palliative Cyberknife Therapy].

A 79-year-old man was diagnosed with retroperitoneal primary unknown cancer recurrence who underwent open fenestration and drainage(because radical cure resection is difficult). Two years after the fenestration, the patient developed severe hip pain and numbness of the right lower limb. Abdominal CT revealed a cystic tumor recurrence extending from the lower abdomen to the right perineum. We selected a palliative cyberknife therapy for pain control. Fractionated radiation using a cyberknife was administered for 5 days(25 Gy in 5 fractions). The hip pain was relieved, and a CT scan showed a reduction in size of the perineal tumor after the cyberknife treatment. The cyberknife therapy may be an effective and promising palliative treatment for patients with pelvic recurrence.

Histamine-releasing factor enhances food allergy.

Food allergy occurs due to IgE- and mast cell-dependent intestinal inflammation. Previously, we showed that histamine-releasing factor (HRF), a multifunctional protein secreted during allergy, interacts with a subset of IgE molecules and that the HRF dimer activates mast cells in an HRF-reactive IgE-dependent manner. In this study, we investigated whether HRF plays any role in food allergy. Specifically, we determined that prophylactic and therapeutic administration of HRF inhibitors that block HRF-IgE interactions reduces the incidence of diarrhea and mastocytosis in a murine model of food allergy. Food allergy-associated intestinal inflammation was accompanied by increased secretion of the HRF dimer into the intestine in response to proinflammatory, Th2, and epithelial-derived cytokines and HRF-reactive IgE levels at the elicitation phase. Consistent with these data, patients with egg allergy had higher blood levels of HRF-reactive IgE compared with individuals that were not hypersensitive. Successful oral immunotherapy in egg-allergy patients and food-allergic mice reduced HRF-reactive IgE levels, thereby suggesting a pathological role for HRF in food allergy. Together, these results suggest that antigen and HRF dimer amplify intestinal inflammation by synergistically activating mast cells and indicate that HRF has potential as a therapeutic target in food allergy.

The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy.

CBP-93872 suppresses maintenance of DNA double-stranded break-induced G2 checkpoint, by inhibiting the pathway between ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) activation. To examine the potential use of CBP-93872 for clinical applications, we analyzed the synergistic effects of platinum-containing drugs, oxaliplatin and cisplatin, pyrimidine antimetabolites, gemcitabine and 5-fluorouracil (5-FU), in combination with CBP-93872, on cell lethality in colorectal and pancreatic cancer cell lines. Treatment with CBP-93872 significantly increased cancer cell sensitivities to various chemotherapeutic agents tested through suppression of checkpoint activation. Our results thus reveal that combination treatment of CBP-93872 with known chemotherapeutic agents inhibits phosphorylation of ATR and Chk1, and induces cell death.