Crystalline morphology of block-copoly(oxypropylene/oxyethylene/oxypropylene) by small-angle X-ray and Raman scattering

Block-copoly(oxypropylene/oxyethylene/oxypropylene)s, with central-block lengths of 39 and 75 oxyethylene units and end-block lengths in the range 1 to 13 oxypropylene units, were investigated in their solid states by small-angle X-ray diffraction and low-frequency Raman spectroscopy, supplemented by differential scanning calorimetry. Low-frequency Raman transitions were assigned to longitudinal modes (LAM) of either unfolded or once-folded chains. The solid state comprised stacked monolayer lamellae in which the chains were usually tilted with respect to the lamellar end plane.     

Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.     

Molecular targeting for epidermal growth factor receptor expressed on breast cancer cells by human fusion protein

Recombinant human ribonuclease 1 (RNasel) was chemically linked to recombinant human epidermal growth factor (EGF). The cytotoxicity of this conjugate was assayed using MTT assay. The EGF-RNase conjugate showed dose-dependent cytotoxicity against breast and squamous cell carcinomas overexpressing the EGF receptor (EGFR). The cytotoxicity of the conjugate correlated positively with the level of EGFR expression by each cell line. These results suggest that the EGF-RNase conjugate is a more effective anticancer agent with less immunogenicity and toxicity than conventional chimeric breast cancer toxins.     

Malignant transformation of aneurysmal bone cyst, with an analysis of the literature

An 11-year-old girl had a lytic, benign-appearing, expansive lesion of the distal tibia radiologically interpreted as an aneurysmal bone cyst (ABC). Tissue from two extensive curettage procedures was also histologically diagnosed as ABC. Approximately 50 months after the onset of symptoms, and 28 months after her last curettage, a highly pleomorphic osteosarcoma developed. The patient had not received prior radiation therapy. The cases in the literature of possible malignant transformation of ABC are reviewed. The authors separate their case from telangiectatic osteosarcoma, and from "aneurysmal bone cyst-like osteosarcoma."     

Gene-specific formation and repair of DNA monoadducts and interstrand cross-links after therapeutic exposure to nitrogen mustards.

PURPOSE: To investigate the possibility of measuring the gene-specific DNA damage after therapeutic exposure to nitrogen mustards and to examine its relationship with the clinical response. EXPERIMENTAL DESIGN: The kinetics of gene-specific monoadducts and interstrand cross-link formation/repair were measured in the p53 and N-ras genes. DNA extracted from human peripheral lymphocytes following in vitro exposure to melphalan or therapeutic exposure to melphalan or cyclophosphamide was used. RESULTS: When lymphocytes were treated in vitro with biologically relevant doses of melphalan, monoadducts accumulated rapidly in both p53 and N-ras genes, reaching maximal levels within 2 h, whereas the highest interstrand cross-link levels were found within 8 h. Thereafter, the adducts were repaired with half-lives of 14.5 +/- 0.3 h (p53) or 18.8 +/- 1.5 h (N-ras) for monoadducts and 12.4 +/- 0.8 h (p53) or 14.1 +/- 2.2 h (N-ras) for interstrand cross-links. Moreover, peak levels of monoadducts in both genes were observed 2 h after treatment in peripheral leukocytes from patients with multiple myeloma treated with high-dose i.v. melphalan, supported by autologous stem cell transplantation, whereas interstrand cross-links were maximal within 8 h. Of seven patients examined, the three who showed the least levels of DNA damage did not respond to the high-dose melphalan. CONCLUSIONS: This is the first report showing that it is feasible to measure gene-specific DNA damage in a readily accessible tissue of humans exposed to bifunctional alkylating drugs and to examine, at the level of the individual patient, the relationships between the induction/repair of cytotoxic DNA damage and clinical response or long-term complications.     

Solitary skeletal hemangioma of the extremities

Objective. To report the clinicopathologic features of solitary skeletal hemangioma of the extremities and to review previous cases in the English language medical literature. Patients. In addition to five of our own cases, 34 literature cases with substantial and 75 with partial clinicopathologic information were found. Results. Our patients, three men and two women, ranged in age from 37 to 83 years (mean 65.6 years). The lesion was an incidental radiologic finding in two patients, while three were symptomatic. In no case was a correct preoperative radiologic diagnosis made, a malignant process being considered as a possibility in all. The hemangiomas were medullary; two involved a metacarpal, two the fibula, and one the humerus. In contrast, previously reported patients were younger (mean age 32 years), predominantly female (60%), and symptomatic in over 90% of cases. The lesion is rare in those younger than age 10 years or older than age 60 years. As in our patients, the long bones are most frequently involved (75%), with the diaphysis or metadiaphysis, as in four of our patients, the most common locations. Although 20% of cases occur in the hands or feet, metacarpal involvement is rare. Medullary origin, as in all of our cases, is most frequent, but 45% of cases are either periosteal (33%) or intracortical (12%). In the literature, cavernous hemangioma is the most frequent type. Three of our hemangiomas were cavernous, one capillary, and one venous, the latter being rarely reported in extremity bones. Conclusions. Due to the diversity of radiologic patterns produced by skeletal hemangioma, a correct preoperative diagnosis is rarely made. Almost all patients do well, even those with less than complete removal of the lesion; local recurrence is rare. All of our patients were well following either therapeutic or simple diagnostic procedures. Due to the destructive nature of some biopsy procedures, the histologic diagnosis of hemangioma may at times also be problematic. Received: 7 February 2000 Revision requested: 31 March 2000 Revision received: 25 May 2000 Accepted: 26 May 2000     

Extent of damage and repair in the p53 tumor-suppressor gene after treatment of myeloma patients with high-dose melphalan and autologous blood stem-cell transplantation is individualized and may predict clinical outcome.

PURPOSE: To quantitate the individual levels of melphalan-induced DNA damage formation and repair in vivo and to search for possible correlations with clinical outcome in patients with multiple myeloma (MM). PATIENTS AND METHODS: The formation and subsequent repair of DNA damage (monoadducts and interstrand cross-links) in the p53 tumor-suppressor gene, the proto-oncogene N-ras, and the housekeeping gene beta-actin during the first 24 hours after treatment with high-dose melphalan (HDM; 200 mg/m2) supported by autologous blood stem-cell transplantation (ABSCT) was measured in blood leukocytes of 26 patients with MM. The peak DNA adduct levels, the total amount of adducts over time, and the rate of adducts repair in each gene were correlated with response and time to progression after HDM. RESULTS: The levels of gene-specific DNA damage formation and the individual repairing capacity varied up to 16-fold among patients, indicating that the melphalan-induced biologic effect in vivo is highly individualized. A significantly greater DNA damage and a slower rate of repair in p53 for all end points under study were found in patients who achieved tumor reduction compared with nonresponding patients. Furthermore, longer progression-free survival correlated with increased peak monoadduct levels in the p53 gene (P = .032). CONCLUSION: Increased DNA damage and slower repairing capacity in the p53 gene from blood leukocytes after HDM correlate with improved outcome of patients with MM who undergo ABSCT. These results suggest that quantitation of such biologic end points may identify patients who are more likely to benefit from this procedure.     

Disability in Older Adults 1: Prevalence,Causes, and Consequences

The effects of disability on an aging population's health and welfare are an important issue in gerontological research. The rapid growth of the elderly population and increases in longevity have led to an ongoing debate about whether longer lives can be matched by longer active lives that are free from disability. After a detailed review of current disability literature, the authors discuss the impact of disability in the elderly, defining disability and reviewing three classes of disability—physical, mental, and social. Both subjective and objective disability measures are described, and disability trends and prevalence rates are reviewed and compared cross culturally, by gender, by age, and over time. The path from chronic disease to disability is described and the consequences of living with disability are discussed in terms of family burdens and the increased need for medical care.