New frontiers in immune checkpoint B7-H3 (CD276) research and drug development.

B7-H3 (CD276), a member of the B7 family of proteins, is a key player in cancer progression. This immune checkpoint molecule is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. In addition to its immune checkpoint function, B7-H3 has been linked to tumor cell proliferation, metastasis, and therapeutic resistance. Furthermore, its drastic difference in protein expression levels between normal and tumor tissues suggests that targeting B7-H3 with drugs would lead to cancer-specific toxicity, minimizing harm to healthy cells. These properties make B7-H3 a promising target for cancer therapy.Recently, important advances in B7-H3 research and drug development have been reported, and these new findings, including its involvement in cellular metabolic reprograming, cancer stem cell enrichment, senescence and obesity, have expanded our knowledge and understanding of this molecule, which is important in guiding future strategies for targeting B7-H3. In this review, we briefly discuss the biology and function of B7-H3 in cancer development. We emphasize more on the latest findings and their underlying mechanisms to reflect the new advances in B7-H3 research. In addition, we discuss the new improvements of B-H3 inhibitors in cancer drug development.

Bacterial profile and antimicrobial susceptibility patterns in cancer patients.

BACKGROUND: Bloodstream infections have been the leading complications in cancer patients because they are at high risk for antibiotic-resistant bacterial infections. There is increasing evidence from different parts of the world of the high prevalence of antimicrobial-resistant bacterial strains in cancer patients. The burden of the infection is high in developing countries, especially in Ethiopia. Data on bacterial profile and antimicrobial susceptibility patterns among cancer patients in Ethiopia is limited. Thus, this study aimed to determine the predominant bacterial species causing bacteremia and their antibiotic resistance pattern among cancer patients at University of Gondar comprehensive specialized hospital. METHODS: A hospital-based, cross-sectional study was conducted on 200 study participants from March to July 2021. All cancer patients who developed a fever at the time of hospital visit were included in this study, and their socio-demographic and clinical data were collected using a structured questionnaire. Blood samples (10 mL for adults and 4 mL for children) were collected from each patient, and the collected blood samples were transferred into sterile tryptic soy broth, then incubated at 37°C for 7 days. Tryptic soy broth which showed signs of growth were Gram-stained and sub-cultured on blood agar, chocolate agar, MacConkey agar, and mannitol salt agar. The inoculated plates were then aerobically incubated at 37°C for 18-24 hours and the isolates obtained were identified using standard microbiological methods. Antimicrobial susceptibility tests were done using a modified Kirby-Bauer disk diffusion technique following CLSI 2021 guidelines. Data were entered using EPI data version 4.6 and analyzed with SPSS version 20. RESULTS: In this study, out of 200 cancer patients included and 67.5% (135/200) of them were males. The majorities of study participants, 56% (113/200) of cancer patients were pediatrics and 26.5% (53/200) of them belong under five years of age. Out of 200 patient samples that had undergone culture, 27% (54/200) samples had bacterial growth. Gram-positive bacterial isolates were predominant, 61.1%, and S. aureus was the predominant Gram-positive isolate, (51.5.6%), followed by coagulase-negative staphylococci (48.5%). Moreover, K. pneumoniae (47%) and P. aeruginosa (29.5%) were the most common Gram-negative bacterial isolates. Among patients who had BSIs, the highest prevalence of BSIs was observed among males (66.7%), and in pediatrics cancer patients (44.2%). Pediatric study participants were more venerable to bloodstream infection (P = 0.000) compared to adult participants. Meropenem (100%), amikacin (100%), piperacillin/tazobactam (72.3%), and ceftazidime (73.5%) were effective against for Gram-negative isolates while cefoxitin (81.2%) and penicillin (70.5%) were effective for Gram-positive isolates. Additionally, most Gram-negative and Gram-positive bacterial isolates were sensitive for gentamycin (75.9%). Multidrug resistance was seen among 17.1% bacterial isolates, and MDR in Gram-negative and Gram-positive bacteria were 83.3% and 16.7%, respectively. Gram-negative bacterial isolates showed a high prevalence of MDR than Gram-positive isolates. CONCLUSIONS AND RECOMMENDATION: BSI's remains an important health problem in cancer patients, and Gram-positive bacteria were more common as etiologic agents of BSIs in cancer patients. S. aureus was the dominant bacteria followed by CoNS, K. pneumoniae, and P. aeruginosa. Multidrug-resistant isolates found in cancer patients and routine bacterial surveillance and study of their resistance patterns may guide successful antimicrobial therapy and improve the quality of care. Therefore, strict regulation of antibiotic stewardship and infection control programs should be considered in the study area.

Inducible Clindamycin and Methicillin Resistant Staphylococcus aureus Among Cancer Patients at University of Gondar Compressive Specialized Hospital, Northwest Ethiopia: Carriage Rate and Antibiotic Resistance Patterns.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a type of Staphylococcus aureus strain which is resistant to a group of beta-lactam antibiotics. Methicillin-resistance is due to a penicillin-binding protein, which has a low affinity for beta-lactam antibiotics. Excess and inappropriate use of clindamycin have led to the emergence of resistant Staphylococcal strains. Cancer patients are at high risk of bacterial colonization due to cancer chemotherapy which leads to severe and prolonged immunosuppression. This study aimed to assess the carriage rate of inducible clindamycin and MRSA among cancer patients. METHODS: A hospital-based cross-sectional study was conducted on 200 cancer patients from January to August 2019. Sociodemographic data and nasal swab samples were collected and inoculated on mannitol salt agar and then incubated at 37°C for 24 hours. The identification of isolates was done by colony characteristics and biochemical reactions. MRSA was detected using cefoxitin disc and inducible clindamycin resistance detected using D-test. Interpretations of antibiotics susceptibility was done using CLSI 2018. Finally, data was entered, cleared, and checked using Epi-info version 7 and exported to SPSS version 20 for analysis. Logistic regression was used for statistical association. p-value ≤ 0.05 at 95% CI was considered statistically significant. RESULTS: In this study, of the 59 Staphylococcus aureus isolates tested, 22% (13/59) were MRSA and 78% (46/59) were MSSA. MRSA carriage rate in females was 18.6% (11/59) whereas in males it was 3.4% (2/59). MRSA carriage among urban residents (15.3% (9/59)) was higher than their rural counterparts (6.8% (4/59)). The prevalence of inducible clindamycin resistance was 17% (10/59). Multi-drug resistance patterns among Staphylococcus aureus isolates was 55.9% (33/59). Clindamycin (84.6%), chloramphenicol (84.6%), and ciprofloxacin (69.2%) were the most effective whereas penicillin (100%), tetracycline (76.9%), and erythromycin (76.9%) were the least effective for MRSA isolates. Urban living, being illiterate, being employed, patients with liver and lung cancer were significantly associated with MRSA carriage. CONCLUSIONS: This study showed high rates of MRSA carriage and inducible clindamycin resistance with the percentages of 22 and 17, respectively. Therefore, decolonization of MRSA carriers and rational usage of antibiotics should be implemented.

Prevalence of Asymptomatic Bacteriuria and Antibiotic Susceptibility Patterns of Bacterial Isolates among Cancer Patients and Healthy Blood Donors at the University of Gondar Specialized Hospital.

BACKGROUND: Urinary tract infections are the common types of infections in the community and health care settings. Despite the widespread availability of antibiotics, urinary tract infection remains a worldwide therapeutic problem. It is a continuous and significant problem in cancer patients. METHODS: A hospital-based comparative cross-sectional study was conducted on 240 study participants from January to June 2019. Sociodemographic data were collected by a predesigned questionnaire and midstream urine samples collected using simple random sampling technique by using clean, sterile plastic cups and then inoculated onto CLED agar plates and incubated at 37°C for 24 hours. Urine culture was considered significant bacteriuria when colony forming units ≥105/mL of voided urine and a single pure colony suspended in nutrient broth and then subcultured onto a blood agar plate and MacConkey agar plate, incubated at 37°C for 24 hours for identification. Identification was done by using standard microbiological methods. Modified Kirby-Bauer disk diffusion technique was applied for antimicrobial susceptibility testing in accordance with CLSI 2018 criteria. Data were entered, cleared, and checked using Epi Info version 7 and exported to SPSS version 20 for analysis. The results were displayed using tables and figures. p value <0.05 at 95% CI was considered as statistically significant. RESULTS: The overall prevalence of asymptomatic bacteriuria in cancer patients was 23.3% while 6.7% in apparently healthy blood donors. E. coli (32.1%) was the commonest isolated uropathogenic bacteria followed by Klebsiella species (25.0%), S. aureus (21.4%), Enterococcus species (10.7%), Serratia species (7.1%), and Enterobacter aerogenes (3.6%) in cancer patients. In apparently healthy blood donors, E. coli, Klebsiella species, and S. aureus were isolated from 75%, 12.5%, and 12.5%, respectively. Most Gram-negative bacteria were more sensitive to ceftazidime, cefoxitin, nalidixic acid, nitrofurantoin, norfloxacin, ciprofloxacin, and tobramycin, whereas highly resistant to ampicillin, penicillin, tetracycline, and ceftazidime. S. aureus isolates were 100% susceptible to nitrofurantoin. CONCLUSIONS: This study showed a high prevalence of asymptomatic bacteriuria among cancer patients (23.3%) compared to apparently healthy blood donors (6.7%). E. coli was isolated predominately. Nitrofurantoin and ciprofloxacin should be used to treat asymptomatic bacteriuria in the study area.