Proline-Hinged α-Helical Peptides Sensitize Gram-Positive Antibiotics, Expanding Their Physicochemical Properties to Be Used as Gram-Negative Antibiotics.

The outer membrane (OM) of Gram-negative bacteria is the most difficult obstacle for small-molecule antibiotics to reach their targets in the cytosol. The molecular features of Gram-negative antibiotics required for passing through the OM are that they should be positively charged rather than neutral, flat rather than globular, less flexible, or more increased amphiphilic moment. Because of these specific molecular characteristics, developing Gram-negative antibiotics is difficult. We focused on sensitizer peptides to facilitate the passage of hydrophobic Gram-positive antibiotics through the OM. We explored ways of improving the sensitizing ability of proline-hinged α-helical peptides by adjusting their length, hydrophobicity, and N-terminal groups. A novel peptide, 1403, improves the potentiation of rifampicin in vitro and in vivo and potentiates most Gram-positive antibiotics. The "sensitizer" approach is more plausible than those that rely on conventional drug discovery methods concerning drug development costs and the development of drug resistance.

Survival with Cemiplimab in Recurrent Cervical Cancer.

BACKGROUND: Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. METHODS: In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. RESULTS: A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. CONCLUSIONS: Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).

Solution to prevent tumor spillage in minimally invasive radical hysterectomy using the endoscopic stapler for treating early-stage cervical cancer: Surgical technique with video.

Gynecologic oncologists had originally preferred minimally invasive surgery (MIS) over laparotomic surgery for patients with early-stage cervical cancer until the Laparoscopic Approach to Cervical Cancer (LACC) trial reported a worse prognosis and more loco-regional recurrence in patients treated with MIS. Although some controversy remains, experts suggested that tumor cell spillage and aggravation may have been caused by intra-corporeal colpotomy, usage of uterine elevators, maintenance of Trendelenburg position, and tumor irritation by capnoperitoneum during surgery. Thus, we introduce a surgical procedure with some steps added to the conventional MIS radical hysterectomy for preventing tumor spillage during the surgery, which is currently being evaluated in terms of safety and efficacy through a prospective, multicenter, single-arm, phase II study, entitled "Safety of laparoscopic or robotic radical surgery using endoscopic stapler for inhibiting tumor spillage of cervical neoplasms (SOLUTION trial: NCT04370496)".

Effects of a web-based expert support self-management program (WEST) for women with breast cancer: A randomized controlled trial.

INTRODUCTION: This study was a randomized controlled trial that examined the effects of a web-based expert support self-management program (WEST) on metabolic syndrome risk factors and self-efficacy among Korean women with breast cancer. METHODS: Participants were 60 women with breast cancer (30 participants each in both the experimental and control groups) who also had metabolic risk factors. WEST is based on the self-efficacy theory and is a self-health management program consisting of a web-based program, DIETEX (which entails keeping a health diary, identifying a lifestyle type, inputting personal health information), and expert support. WEST was provided to the experimental group once a week for 24 weeks. Metabolic syndrome risk factors and self-efficacy of the experimental and control groups were examined pre-intervention and at 12 and 24 weeks after intervention. RESULTS: The decreases in body fat, body fat percentage, and waist circumference were greater in the experimental group than in the control group at 24 weeks (p = 0.019, p = 0.025, and p = 0.038, respectively). DISCUSSION: The present study can provide basic data for the development and application of interventions for women with breast cancer in the future. Additionally, we propose that WEST be included in the treatment process to complement the intervention of medical personnel for improving metabolic risk factors in women with breast cancer.

Characterization of Metabolic Syndrome Risk Factors and Health-Related Behaviors in Korean Patients With Breast Cancer by Abdominal Obesity Status.

BACKGROUND: Breast cancer is the second most prevalent malignancy among Korean women. Changes in lifestyle during and after remission of breast cancer tend to increase abdominal visceral fat, leading to increased risks of metabolic syndrome and chronic diseases. PURPOSE: This cross-sectional study examined the differences in metabolic syndrome risk factors and health-related behaviors between abdominally obese and nonabdominally obese groups of Korean patients with breast cancer. METHODS: The participants were assigned to nonabdominal obesity (waist circumference < 85 cm, n = 77) and abdominal obesity (waist circumference ≥ 85 cm, n = 59) groups, and a questionnaire was used to assess the prevalence of risk factors of metabolic syndrome and health-related behaviors in each. The chi-square test and t test were used to analyze the data. RESULTS: The average age was 54.2 years in the abdominal obesity group and 51.3 years in the nonabdominal obesity group. The average blood pressure and fasting blood glucose levels were higher in the abdominal obesity than the nonabdominal obesity group (117.3/76.3 vs. 108.9/70.4 mmHg, respectively [p = .001]; 96.9 and 90.1 mg/dl, respectively [p = .007]). High-density lipoprotein cholesterol was lower in the abdominal obesity than the nonabdominal obesity group (55.4 and 62.5 mg/dl, respectively [p = .005]), whereas triglycerides were higher in the abdominal obesity than the nonabdominal obesity group (151.6 and 111.3 mg/dl, respectively [p = .006]). The prevalence of metabolic syndrome in the abdominal obesity and nonabdominal obesity groups were 42.4% and 9.1%, respectively (p = .001). Moreover, eating habits differed between the two groups, with the frequency of vegetable consumption lower in the abdominal obesity than the nonabdominal obesity group (p = .040) and the frequencies of salty and sweet food consumption and of overeating higher in the abdominal obesity than the nonabdominal obesity group. The percentage of participants who exercised for 30 minutes three times per week was 52.5% in the abdominal obesity group and 71.4% in the nonabdominal obesity group (p = .024). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This observational study found more metabolic syndrome risk factors in the abdominal obesity group than the nonabdominal obesity group. Consumption of sweet foods and overeating were higher and the frequencies of vegetable intake and exercise were lower in the abdominal obesity group. These findings suggest that female abdominally obese patients with breast cancer exhibit health-related behaviors that require improvement and better management. Interventional programs should be developed based on the findings of this study to reduce cancer recurrence and mortality in patients with breast cancer.

Tumor evolution and chemoresistance in ovarian cancer.

Development of novel strategies to overcome chemoresistance is central goal in ovarian cancer research. Natural history of the cancer development and progression is being reconstructed by genomic datasets to understand the evolutionary pattern and direction. Recent studies suggest that intra-tumor heterogeneity (ITH) is the main cause of treatment failure by chemoresistance in many types of cancers including ovarian cancer. ITH increases the fitness of tumor to adapt to incompatible microenvironment. Understanding ITH in relation to the evolutionary pattern may result in the development of the innovative approach based on individual variability in the genetic, environment, and life style. Thus, we can reach the new big stage conquering the cancer. In this review, we will discuss the recent advances in understanding ovarian cancer biology through the use of next generation sequencing (NGS) and highlight areas of recent progress to improve precision medicine in ovarian cancer.

Prognostic implication of the metastatic lesion-to-ovarian cancer standardised uptake value ratio in advanced serous epithelial ovarian cancer.

OBJECTIVES: To evaluate the prognostic value of metabolic activity of metastatic lesions measured by 18F-flurodeoxyglucose (18F-FDG) uptake on preoperative positron emission tomography/computed tomography (PET/CT) in patients with advanced serous epithelial ovarian cancer (EOC). METHODS: Clinico-pathological variables and PET/CT parameters such as the maximum standardised uptake value of the ovarian cancer (SUVovary), metastatic lesions (SUVmeta), and the metastatic lesion-to-ovarian cancer standardised uptake value ratio (SUVmeta/SUVovary) were assessed in International Federation of Gynaecology and Obstetrics (FIGO) stage III, IV patients. RESULTS: Clinico-pathological data were retrospectively reviewed for 94 eligible patients. The median progression-free survival (PFS) was 18.5 months (range, 6-90 months), and 57 (60.6%) patients experienced recurrence. Older age [P = 0.017, hazard ratio (HR) 1.036, 95% CI 1.006-1.066], residual disease after surgery (P = 0.024, HR 1.907, 95% CI 1.087-3.346), and high SUVmeta/SUVovary (P = 0.019, HR 2.321, 95% CI 1.148-4.692) were independent risk factors of recurrence. Patients with high SUVmeta/SUVovary showed a significantly worse PFS than those with low SUVmeta/SUVovary (P = 0.007, log-rank test). CONCLUSIONS: Preoperative SUVmeta/SUVovary was significantly associated with recurrence and has an incremental prognostic value for PFS in patients with advanced serous EOC. KEY POINTS: • The prognostic value of the metabolic activity of metastatic lesions was investigated. • SUVmeta/SUVovary was significantly associated with recurrence of serous EOC. • Preoperative SUVmeta/SUVovary can be a predicator of serous EOC recurrence.

Sodium Bicarbonate Solution versus Chlorhexidine Mouthwash in Oral Care of Acute Leukemia Patients Undergoing Induction Chemotherapy: A Randomized Controlled Trial.

PURPOSE: The objective of this study was to compare the effectiveness of sodium bicarbonate (SB) solution with chlorhexidine (CHX) mouthwash in oral care of acute leukemia patients under induction chemotherapy. METHODS: Forty-eight patients were randomly selected and assigned to an SB solution group or CHX-based product group according to acute myelogenous leukemia or acute lymphoblastic leukemia. Patients were asked to rinse their mouth four times a day from the day before chemotherapy started until discharge. The World Health Organization mucositis grade, patient-reported Oral Mucositis Daily Questionnaire, and clinical signs associated with infection were assessed on a daily basis. The oral microbial count was assessed on a weekly basis from the 1st day of chemotherapy started to the 28th day or to the day of discharge from the hospital. RESULTS: Of all the patients in the SB group, 25.0% developed ulcerative oral mucositis, whereas 62.5% in the CHX group did. The onset of oral mucositis was later in the SB group than the CHX group. The oral bacterial colonization in the SB group was significantly higher than that in the CHX group, but clinical signs associated with infection did not differ in both groups. CONCLUSION: As a result of this study, it was found that oral care by SB solution for acute leukemia patients undergoing chemotherapy was an effective intervention to improve oral health.

Silencing of NbBTF3 results in developmental defects and disturbed gene expression in chloroplasts and mitochondria of higher plants.

BTF3 (betaNAC) was originally isolated as a general transcription factor required for RNA polymerase II-dependent transcription, and later found to be a beta-subunit of nascent-polypeptide-associated complex that has been implicated in regulating protein localization during translation. In this study, virus-induced gene silencing of NbBTF3 encoding a Nicotiana benthamiana homolog of human BTF3 caused leaf yellowing and abnormal leaf morphology without altering the overall growth of the plant. The NbBTF3 gene is constitutively expressed and the NbBTF3-GFP fusion protein is primarily targeted to the nucleus. At the cellular level, downregulation of NbBTF3 expression reduced the chloroplast sizes and chlorophyll contents. The affected cells produced excessive amounts of reactive oxygen species. Furthermore, the transcript level of various plastid- and mitochondria-encoded genes was severely reduced in the NbBTF3-depleted leaf cells. These findings indicate that depletion of NbBTF3 activity preferentially affected development and/or physiology of chloroplasts and mitochondria in plants, possibly by hampering efficient translocation of the nascent organellar proteins into the organelles.

Effects of a relaxation breathing exercise on anxiety, depression, and leukocyte in hemopoietic stem cell transplantation patients.

This study was performed to investigate the effects of a relaxation breathing exercise on anxiety, depression, and leukocyte count in patients who underwent allogenic hemopoietic stem cell transplantation. Thirty-five patients were randomly selected, with 18 assigned to an exercise group and 17 assigned to a control group. The exercise intervention was applied to the exercise group for 30 minutes every day for 6 weeks. It consisted of physical exercises combined with relaxation breathing. Anxiety was measured by the State-Trait Anxiety Inventory and depression was measured by the Beck Depression Inventory. The total number of leukocytes was calculated from total and differential counts of peripheral white blood cells. The exercise group had a greater decrease in anxiety and depression than did the control group, but the total number of leukocytes did not significantly differ between the two groups. These findings indicate that a relaxation breathing exercise would improve anxiety and depression levels in patients who undergo allogenic hemopoietic stem cell transplantation, but would not affect the number of leukocytes.

Effects of a relaxation breathing exercise on fatigue in haemopoietic stem cell transplantation patients.

AIM: Our purpose was to investigate the effect of a relaxation breathing exercise on fatigue in allogenic haemopoietic stem cell transplantation patients. BACKGROUND: Exercise is a promising approach in ameliorating the fatigue associated with cancer and its treatment. DESIGN: A randomized design with control, experimental groups being assessed pre- and postintervention. METHODS: Thirty-five patients were randomly selected, with 18 assigned to an exercise group and 17 to a control group. The exercise intervention lasted for 30 minutes every day for six weeks. It consisted of physical exercise combined with relaxation breathing exercise. Fatigue was measured by the revised version of the Piper Fatigue Scale. RESULTS: The exercise group had a greater decrease in fatigue than the control group. CONCLUSION: These findings indicate that a relaxation breathing exercise would improve fatigue in allogenic haemopoietic stem cell transplantation patients. RELEVANCE TO CLINICAL PRACTICE: A relaxation breathing exercise by a nurse can improve fatigue in allogenic haemopoietic stem cell transplantation patients.

[The comparison of the stress and coping methods of cancer patients and their caregivers].

PURPOSE: The purpose of this study was to identify the stress and the coping methods in the cancer patients and their caregivers. METHOD: The stress method was measured by VAS(Visual Analogue Scale). The coping methods was measured using the modified Ways of Coping Questionnaire. The phases of patient illness consisted of 1st(initial) stage, and 2nd(recurred) stage and 3rd(terminal) stage based on Lewandowski & Jones(1988) method. The data were collected by a survey of convenience sampling of 257 cancer patients and 196 of their caregivers from two hospitals in Seoul. The data were analyzed using paired t-test, unpaired t-test. RESULT: The stress level of cancer patients was lower than their caregivers. The cancer patients used emotion-focused coping mode than problem-focused coping mode. The caregivers problem-focused coping mode over emotion-focused coping mode. In the problem-focused coping mode, the caregivers significantly used two coping strategies that were 'positive cope', 'information seeking' more than patients. In emotion-focused coping mode, the caregivers significantly used one coping strategies that was 'wish' more than patients. The patients tended to used two coping strategies that were 'blame' and 'emotion expression' more than the caregivers. CONCLUSION: Further study needs to be done to positively identify these coping methods and develop interventions to assist patients and their caregivers.

Stress and coping strategies of patients with cancer. A Korean study.

Cancer is a potential life-threatening illness that engenders considerable psychologic distress, requiring persistent coping for the treatment procedures. In this cross-sectional descriptive study stress levels and coping strategies of 257 cancer patients residing in South Korea are addressed. Lazarus and Folkman's theory of stress and coping was used as the theoretical framework. The data were collected from November 1999 to March 2000 by face-to-face interviews. Study participants were primarily male (62.6%) and married (91.4%). Cancer of the gastrointestinal system was the most prevalent type of cancer (31.3%). Women and the patients in the third-stage of cancer showed higher stress but less coping than other groups. Stress was negatively correlated with both problem-focused coping and emotion-focused coping. Korean patients with cancer used emotion-focused coping strategies more than problem-focused coping strategies.