Emerging Immunotherapies against Novel Molecular Targets in Breast Cancer

Immunotherapy is a highly emerging form of breast cancer therapy that enables clinicians to target cancers with specific receptor expression profiles. Two popular immunotherapeutic approaches involve chimeric antigen receptor-T cells (CAR-T) and bispecific antibodies (BsAb). Briefly mentioned in this review as well is the mRNA vaccine technology recently popularized by the COVID-19 vaccine. These forms of immunotherapy can highly select for the tumor target of interest to generate specific tumor lysis. Along with improvements in CAR-T, bispecific antibody engineering, and therapeutic administration, much research has been done on novel molecular targets that can especially be useful for triple-negative breast cancer (TNBC) immunotherapy. Combining emerging immunotherapeutics with tumor marker discovery sets the stage for highly targeted immunotherapy to be the future of cancer treatments. This review highlights the principles of CAR-T and BsAb therapy, improvements in CAR and BsAb engineering, and recently identified human breast cancer markers in the context of in vitro or in vivo CAR-T or BsAb treatment.     

DNA bending by a phantom protein

BACKGROUND: Despite its stiffness, duplex DNA is extensively bent and folded during packaging and gene expression in biological systems. Modulation of the electrostatic repulsion between phosphates in the DNA backbone may be important in the bending of DNA by proteins. Here, we analyze the shape of DNA molecules that have been modified chemically to mimic the electrostatic consequences of a bound protein. RESULTS: We have simulated salt bridges between DNA phosphates and cationic amino acid sidechains of a phantom protein by tethering ammonium cations to one face of the DNA helix. Tethered ammonium cations, but not neutral acetylated controls, induce DNA to bend toward its neutralized surface. CONCLUSIONS: The shape of DNA molecules bearing a laterally-asymmetric distribution of tethered cations agrees qualitatively with theoretical predictions and with results previously obtained using neutral phosphate analogs. These data suggest principles that might be applied to the design of artificial DNA-bending proteins.     

The “SOMSEM”—An SEM-based scanning optical microscope

No one form of microscopy is ideal for all applications and, in general, significant advances are made by correlating several techniques. In this paper, a scanning optical microscope is discussed which is based on the SEM and is entirely compatible with it. This new hybrid instrument, known as the SOMSEM, has been demonstrated using a converted SEM specimen stage and a standard Cambridge Stereoscan 250 Mk II microscope. The operating principles have been verified, and silicon MOS (metal oxide semiconductor) devices have been successfully imaged using the OBIC (optical beam induced current) mode thus avoiding electron beam damage. Potential applications and future developments are briefly discussed.     

Independent segregation of von Hippel-Lindau disease and cerebral cavernomas

A probable diagnosis of von Hippel-Lindau disease was made in a two generation family in which the proband had a phaeochromocytoma, renal cysts, and multiple cerebral cavernomas. His sister had multiple similar cerebral vascular lesions and his father died from renal carcinoma aged 42. Although the family did not satisfy the conventional diagnostic criteria for von Hippel-Lindau disease, an underlying germline mutation in the von Hippel-Lindau disease tumour suppressor gene was identified in the proband. Molecular genetic analysis not only confirmed the putative diagnosis of the disease in the proband but also showed that the cerebral vascular lesions segregated independently from the von Hippel-Lindau disease mutation. This report exemplifies how molecular genetic investigations can enhance the diagnosis and management of families with suspected von Hippel-Lindau disease, particularly when the manifestations, as in this family, are not typical.     

Ultra-shallow raised p+−n junctions formed by diffusion from selectively depositedIn-situ doped Si0.7Ge0.3

In this paper, a novel raised p⁺−n junction formation technique is presented. The technique makes use ofin- situ doped, selectively deposited Si_0.7Ge_0.3 as a solid diffusion source. In this study, the films were deposited in a tungsten halogen lamp heated cold-walled rapid thermal processor using SiCl₂H₂, GeH₄, and B₂H₆. The microstructure of the Si_0.7Ge_0.3 layer resembles that of a heavily defected epitaxial layer with a high density of misfit dislocations, micro-twins, and stacking faults. Conventional furnace annealing or rapid thermal annealing were used to drive the boron from thein- situ doped Si_0.7Ge_0.3 source into silicon to form ultra-shallow p⁺−n junctions. Segregation at the Si_0.7Ge_0.3/Si interface was observed resulting in an approximately 3:1 boron concentration discontinuity at the interface. Junction profiles as shallow as a few hundred angstroms were formed at a background concentration of 10¹⁷ cm⁻³.     

Dietary fat and sex modify heterozygote effects of the rat fatty (fa) allele

Rats carrying one copy of the obesity gene fa may exhibit intermediate phenotypes between lean (+/+) and homozygous mutants (fa/fa). Previous data suggested to us that fa heterozygotes may be more sensitive than wild-type rats to high fat diets. To test this hypothesis, we generated +/+ and fa/+ rats and fed them diets containing 12% or 48% energy as fat for 7 wk. Energy efficiency was significantly greater in males than in females and in high fat-fed vs. low fat-fed rats. Perirenal fat pad weights were significantly greater in males than in females, in high fat-vs. low fat-fed rats and in fa/+ vs. +/+ rats. Adipose and soleus plasma membrane calcium-ATPase concentrations were significantly lower in rats fed the high fat diet. This protein was also lower in soleus of fa/+ rats compared with +/+ rats. There were significant diet x genotype interactions such that the high fat diet had the greatest effect on fat pads and calcium-ATPase in fa/+ rats. The results of the present study show heterozygote effects of the fa allele and suggest that these effects may be modulated by both sex-related factors and dietary manipulation.     

Long-term Renters in the Australian Housing Market

The paper provides the first examination into the characteristics and housing circumstances of long-term private renters in Australia. It utilises a national sample of 4677 private renter households drawn from the 1994 ABS Survey of Rental Tenants. In Australia 40 per cent of private renters are identified as 'long-term renters', defined as having rented for more than 10 years. Two main types of long-term renters are examined: 'continuals' who have rented continuously since leaving the parental home, and 'returners' who have resumed renting after a period as a home purchaser, but cumulatively have rented for more than 10 years. Continuals, in contrast to returners, are characterised mainly by lower household incomes and higher unemployment. Returners, on the other hand, are more diverse socio-economically, older than other private renters, and more likely to have experienced marital breakdown. Long-term renters (both continuals and returners) change residence less frequently (although still at a rate double the national average). Rental conditions also vary between long and shorter-term groups. Long-term renters appear to be in a less form alised sector of the market. They are less likely than shorter-term renters to rent from estate agents, pay a bond, hold a lease, or pay rent in advance. The findings in this paper challenge the traditional view of private rental as predom inantly a short-term, transitional tenure.     

Review of Innovation up close: How school improvement works.

Reviews the book, Innovation up close: How school improvement works by A. Michael Huberman and Matthew B. Miles (1984). In this volume, Huberman and Miles address the matter of how to improve schools by means of 12 case studies of improvement efforts in elementary and secondary school districts in the United States. They provide a richly detailed, scholarly, yet highly practical account of what seems to transpire when educators and related professionals seek to improve schools. Among the psychologically relevant school improvement factors examined are the incentives and roles of administrators, teachers, students, and communities in the success and failure of a variety of innovative programs. The authors achieve what they set out to do: report about how school improvement seems to occur, based on empirical investigation, and relate their findings to prior work and fundamental concepts of school improvement. The book provides considerable substantive insights. This book is highly recommended because it is a superb blend of theory, practice, and research in the complex domain of the school. (PsycINFO Database Record (c) 2010 APA, all rights reserved)