PET/MRI and Novel Targets for Breast Cancer.

Breast cancer, with its global prevalence and impact on women's health, necessitates effective early detection and accurate staging for optimal patient outcomes. Traditional imaging modalities such as mammography, ultrasound, and dynamic contrast-enhanced magnetic resonance imaging (MRI) play crucial roles in local-regional assessment, while bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) aid in evaluating distant metastasis. Despite the proven utility of 18F-FDG PET/CT in various cancers, its limitations in breast cancer, such as high false-negative rates for small and low-grade tumors, have driven exploration into novel targets for PET radiotracers, including estrogen receptor, human epidermal growth factor receptor-2, fibroblast activation protein, and hypoxia. The advent of PET/MRI, which combines metabolic PET information with high anatomical detail from MRI, has emerged as a promising tool for breast cancer diagnosis, staging, treatment response assessment, and restaging. Technical advancements including the integration of PET and MRI, considerations in patient preparation, and optimized imaging protocols contribute to the success of dedicated breast and whole-body PET/MRI. This comprehensive review offers the current technical aspects and clinical applications of PET/MRI for breast cancer. Additionally, novel targets in breast cancer for PET radiotracers beyond glucose metabolism are explored.

Association Between Oral Health Status and Survival Time in Terminally Ill Cancer Patients.

INTRODUCTION: Patients with terminal cancer often experience various oral problems. Whether oral health status is associated with the survival of terminally ill cancer patients receiving palliative care remains unclear. METHODS: We analyzed the data of 59 Korean patients with terminal cancer receiving palliative care, including their oral health status, using a modified Korean version of the Oral Health Assessment Tool (OHAT). Patients were categorized into "Good," "Moderate," or "Poor" groups based on OHAT scores. The Kaplan-Meier method was used to compare the median survival time, and the prognosis between groups was estimated using Cox proportional hazard models. RESULTS: The most common oral symptoms observed were xerostomia (69.5%) and mucositis (17.0%). Significantly shorter survival times were observed in patients with hyperbilirubinemia, elevated creatinine levels, and no use of dentures. The "Poor" group had a shorter survival than the "Good" oral group (P = .010). A multivariate Cox proportional hazards analysis revealed that the "Poor" group was significantly associated with poor survival compared to the "Good" group (hazard ratio, 2.05; P = .047). CONCLUSION: Terminally ill cancer patients with poor oral health may have a higher risk of shorter survival. Palliative care professionals should pay attention to oral health. Further research is needed to determine the effects of oral care on survival.

FDG PET/CT to Predict Recurrence of Early Breast Invasive Ductal Carcinoma.

This study investigated the prognostic value of FDG PET/CT radiomic features for predicting recurrence in patients with early breast invasive ductal carcinoma (IDC). The medical records of consecutive patients who were newly diagnosed with primary breast IDC after curative surgery were reviewed. Patients who received any neoadjuvant treatment before surgery were not included. FDG PET/CT radiomic features, such as a maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), skewness, kurtosis, entropy, and uniformity, were measured for the primary breast tumor using LIFEx software to evaluate recurrence-free survival (RFS). A total of 124 patients with early breast IDC were evaluated. Eleven patients had a recurrence (8.9%). Univariate survival analysis identified large tumor size (>2 cm, p = 0.045), high Ki-67 expression (≥30%, p = 0.017), high AJCC prognostic stage (≥II, p = 0.044), high SUVmax (≥5.0, p = 0.002), high MTV (≥3.25 mL, p = 0.044), high TLG (≥10.5, p = 0.004), and high entropy (≥3.15, p = 0.003) as significant predictors of poor RFS. After multivariate survival analysis, only high MTV (p = 0.045) was an independent prognostic predictor. Evaluation of the MTV of the primary tumor by FDG PET/CT in patients with early breast IDC provides useful prognostic information regarding recurrence.

Anti-Tumor Effects of Sodium Meta-Arsenite in Glioblastoma Cells with Higher Akt Activities.

Glioblastoma is a type of aggressive brain tumor that grows very fast and evades surrounding normal brain, lead to treatment failure. Glioblastomas are associated with Akt activation due to somatic alterations in PI3 kinase/Akt pathway and/or PTEN tumor suppressor. Sodium meta-arsenite, KML001 is an orally bioavailable, water-soluble, and trivalent arsenical and it shows antitumoral effects in several solid tumor cells via inhibiting oncogenic signaling, including Akt and MAPK. Here, we evaluated the effect of sodium meta-arsenite, KML001, on the growth of human glioblastoma cell lines with different PTEN expression status and Akt activation, including PTEN-deficient cells (U87-MG and U251) and PTEN-positive cells (LN229). The growth-inhibitory effect of KML001 was stronger in U87-MG and U251 cells, which exhibited higher Akt activity than LN229 cells. KML001 deactivated Akt and decreased its protein levels via proteasomal degradation in U87-MG cells. KML001 upregulated mutant PTEN levels via inhibition of its proteasomal degradation. KML001 inhibited cell growth more effectively in active Akt-overexpressing LN229 cells than in mock-expressing LN229 cells. Consistent with these results, KML001 sensitized PTEN-deficient cells more strongly to growth inhibition than it did PTEN-positive cells in prostate and breast cancer cell lines. Finally, we illustrated in vivo anti-tumor effects of KML001 using an intracranial xenograft mouse model. These results suggest that KML001 could be an effective chemotherapeutic drug for the treatment of glioblastoma cancer patients with higher Akt activity and PTEN loss.

Mechanical Properties of Single Muscle Fibers: Understanding Poor Muscle Quality in Older Adults with Diabetes.

BACKGROUND: While aging causes muscle weakness, type 2 diabetes mellitus (T2DM) is also considered a high-risk factor for the induction of skeletal muscle weakness. Previous studies have reported increased collagen content in insulin-resistant skeletal muscles. Here, we studied the mechanical properties of aged skeletal muscle in subjects with T2DM to investigate whether aged skeletal muscles with T2DM induce higher passive tension due to the abundance of extracellular matrix (ECM) inside or outside of the muscle fibers. METHODS: Samples from the gluteus maximus muscles of older adults with diabetes (T2DM) and non-diabetic (non-DM) older adults who underwent elective orthopedic surgery were collected. Permeabilized single muscle fibers from these samples were used to identify their mechanical properties. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to quantify titin and fiber type distributions in these samples. RESULTS: We confirmed a significant predominance of type I fiber ratio in both T2DM and non-DM aged muscles. While the average cross-sectional area and maximal active tension of the single fibers were smaller in the T2DM group than those in the non-DM group, the difference was not statistically significant. T2DM subjects showed significantly greater passive tension and lower titin-/ECM-based passive tension ratios than those in non-DM subjects, which indicated that more ECM but less titin contributed to the total passive tension. CONCLUSION: Based on our findings, we concluded that T2DM may cause increased passive stiffness of single skeletal muscle fibers in older adults because of an excessive accumulation of ECM in and around single muscle fibers due to increased insulin resistance.

The combination of area under the curve and percentage change in estimated glomerular filtration rate predicts long-term outcome of kidney transplants.

The development of surrogate markers for long-term outcomes of kidney transplant (KT) is a focus of attention. We examined the possibility of using a combination of the area under the curve of estimated glomerular filtration rate (eGFR) for 2 years (AUCeGFR2yrs ) and percent change in eGFR between 1 and 2 years after KT (% changeeGFR1/2yr ) as a surrogate marker. We compared the predictive power of death-censored graft failure with various combinations. The combination of >2% vs ≤2% for % changeeGFR1/2yr and >1300 vs ≤1300 mL/min/month for AUCeGFR2yr had the highest Harrell C-index (0.647; 95% confidence interval [95% CI], 0.604-0.690). The death-censored graft survival rate of the group with ≤2% changeeGFR1/2yr and ≤1300 mL/min/month AUCeGFR2yr was significantly lower than those of other groups. The AUC/% change eGFR had comparable predictive power to the previously identified marker ≥30% decline in eGFR between years 1 and 3 after KT (≤-30% changeeGFR1/3yr ) (Harrell's C-index = 0.645 [95% CI 0.628-0.662] for ≤-30% changeeGFR1/3yr ). The proposed combination might be useful as a surrogate marker in KT trials because it requires a shorter surveillance period than the established marker while having comparable predictive power.

Radioembolization for the Treatment of Primary and Metastatic Liver Cancers.

Radioembolization using 90Y microspheres (glass or resin) has been introduced as an effective intraarterial therapy for unresectable primary and metastatic liver cancers. Although the basic therapeutic effect of chemoembolization results from ischemia, the therapeutic efficacy of radioembolization comes from radiation. Furthermore, compared with surgical resection and local ablation therapy, radioembolization is available with less limitation on the sites or number of liver cancers. The radioisotope 90Y is a ß-radiation emitter without γ-radiation, with the emission of secondary bremsstrahlung photons and small numbers of positrons. Administration of 90Y microspheres into the hepatic artery can deliver a high dose of radiation selectively to the target tumor with limited radiation exposure to the surrounding normal parenchyma, and has low systemic toxicity. In general, radioembolization has been considered for patients with unresectable primary or metastatic liver-only or liver-dominant cancers with no ascites or other clinical signs of liver failure, life expectancy of > 12 weeks, and good performance status. Here, we review the current radioactive compounds, pretreatment assessment, and indications for radioembolization in patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and liver metastases from colorectal cancer.

Two-Photon Probe for TNF-α. Assessment of the Transmembrane TNF-α Level in Human Colon Tissue by Two-Photon Microscopy.

We developed Pyr1-infliximab: a two-photon probe for TNF-α. Pyr1-infliximab showed absorption maxima at 280 and 438 nm and an emission maximum at 610 nm in an aqueous buffer and effective two-photon action cross-section values of (520-2830) × 10-50 cm4s/photon in RAW 264.7 cells. After this probe was labeled, it was possible to detect Pyr1-infliximab-transmembrane TNF-α complexes in a live cell and to determine the relative proportion of these complexes in human colon tissues. This proportion among healthy, possibly inflamed, and inflamed tissues of patients with ulcerative colitis was found to be 1.0/4.5/10. This probe may find useful applications for selective detection of transmembrane TNF-α in a live cell or tissue, for quantification of inflammation in human colon tissue or of antidrug antibodies in patients who stop responding to anti-TNF therapy, and for monitoring of the response to this therapy.

Influence of Supplementary Vitamin D on Bone Mineral Density When Used in Combination with Selective Estrogen Receptor Modulators.

OBJECTIVES: Vitamin D is regarded as one of the major nutrients that significantly influence bone metabolism. This study aims to look at the effect of supplementary vitamin D on bone mineral density (BMD) in female osteoporosis patients. METHODS: The retrospective hospital record review was performed on 282 patients who were diagnosed with osteoporosis and treated with selective estrogen receptor modulators (SERMs) between January 2015 and December 2016. Of these patients, 151 were treated with SERMs only while 131 were treated using both SERMs and vitamin D supplements. The BMD and any occurrence of osteoporotic fracture episode were investigated after one year. The result of two groups was compared to find the significance of vitamin D. RESULTS: Overall, improvement in BMD score was observed in 76% of the patients. The BMD of the SERMs only group improved by 3% in spine and 1% in the hip while that of the SERMs with vitamin D group improved by 6% and 1% respectively. Statistical significance was noticed in the spine only. One distal radius fracture and one single level vertebral fracture occurred in patients of SERMs group while two distal radius fractures occurred in SERMs with vitamin D group. There was no occurrence of around hip fracture in both groups. CONCLUSION: The result of the current study suggests that additional vitamin D may have some additive effect on improving BMD of the spine. Further study with the larger study population and the extended study period is recommended.

Umbilical cord/placenta-derived mesenchymal stem cells inhibit fibrogenic activation in human intestinal myofibroblasts via inhibition of myocardin-related transcription factor A.

BACKGROUND: The lack of anti-fibrotic agents targeting intestinal fibrosis is a large unmet need in inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Previous studies have found that perinatal tissue (umbilical cord, UC; placenta, PL)-derived mesenchymal stem cells (MSCs) reduce fibrosis in several organs. However, their effects on human intestinal fibrosis are poorly understood. This study investigated the anti-fibrogenic properties and mechanisms of MSCs derived from UC and PL (UC/PL-MSCs) on human primary intestinal myofibroblasts (HIMFs). METHODS: The HIMFs were treated with TGF-ß1 and co-cultured with UC/PL-MSCs. We used a small molecular inhibitor CCG-100602 to examine whether serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factor A (MRTF-A) are involved in TGF-ß1-induced fibrogenic activation in HIMFs. The anti-fibrogenic mechanism of UC/PL-MSCs on HIMFs was analyzed by detecting the expression of RhoA, MRTF-A, and SRF in HIMFs. RESULTS: UC/PL-MSCs reduced TGF-ß1-induced procollagen1A1, fibronectin, and α-smooth muscle actin expression in HIMFs. This anti-fibrogenic effect was more apparent in the UC-MSCs. TGF-ß1 stimulation increased the expressions of RhoA, MRTF-A, and SRF in the HIMFs. TGF-ß1 induced the synthesis of procollagen1A1, fibronectin, and α-smooth muscle actin through a MRTF-A/SRF-dependent mechanism. Co-culture with the UC/PL-MSCs downregulated fibrogenesis by inhibition of RhoA, MRTF-A, and SRF expression. CONCLUSIONS: UC/PL-MSCs suppress TGF-ß1-induced fibrogenic activation in HIMFs by blocking the Rho/MRTF/SRF pathway and could be considered as a novel candidate for stem cell-based therapy of intestinal fibrosis.

EGF receptor stimulation shifts breast cancer cell glucose metabolism toward glycolytic flux through PI3 kinase signaling.

Breast cancers that express epidermal growth factor (EGF) receptors (EGFRs) are associated with poor prognosis. Our group recently showed in breast cancer patients that EGFR expression is strongly correlated with high tumor uptake of the glucose analogue, 18F-fluorodeoxyglucose (FDG). Here, we explored the cellular mechanism and signaling pathways that can explain the relation between EGFR and breast cancer cell glucose metabolism. FDG uptake, lactate production and hexokinase (HK) activity were measured, and proliferation assays and western blots were performed. EGF stimulated an increase of FDG uptake in EGFR-positive T47D and MDA-MB-468 cells, but not in MCF-7 cells. In T47D cells, the effect was dose-dependent and was accompanied by increased lactate production, indicating a shift toward glycolytic flux. This metabolic response occurred through enhanced HK activity and upregulated glucose transporter 1 (GLUT1) expression. EGFR stimulation also increased T47D cell proliferation. Blocking EGFR activation with BIBX1382 or gefitinib completely abolished both FDG uptake and proliferation effects. EGFR stimulation induced MAP kinase (MAPK) and PI3 kinase (PI3K) activation. Increased cell proliferation by EGFR stimulation was completely abolished by MAPK inhibition with PD98059 or by PI3K inhibition with LY294002. Increased FDG uptake was also completely abrogated by PI3K inhibition but was uninfluenced by MAPK inhibition. These findings suggest that the association between breast tumor EGFR expression and high FDG uptake might be contributed by stimulation of the PI3K pathway downstream of EGFR activation. This was in contrast to EGFR-mediated cell proliferation that required MAPK as well as PI3K signaling.

Radiation-Induced CXCL12 Upregulation via Histone Modification at the Promoter in the Tumor Microenvironment of Hepatocellular Carcinoma.

Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive CD133+/CD24- cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

Radiation-Induced CXCL12 Upregulation via Histone Modification at the Promoter in the Tumor Microenvironment of Hepatocellular Carcinoma.

Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive CD133+/CD24- cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

Effects of cisplatin on photosensitizer-mediated photodynamic therapy in breast tumor-bearing nude mice.

OBJECTIVE: This study aimed to evaluate the potential effects of cisplatin on photodynamic therapy (PDT) in breast cancer using a breast tumor-bearing mouse model. METHODS: In this study, breast tumor (experimental mammary tumour-6 cell)-bearing nude mice were used as experimental animals. Photolon® (photosensitizer, 2.5 mg/kg body weight [BW]) was injected intraperitoneally; after 2 hours, the tumors were irradiated (660 nm, 80 J/cm2) using a diode laser tool. Cisplatin (3 mg/kg BW) was injected intraperitoneally 1 hour before the Photolon® injection. RESULTS: Tumor volume increased over time in the control group and was not different from that in the cisplatin group. In the PDT group, the tumor volume increased on day 3, but not on day 7. In the cisplatin+PDT group, tumor volume increased on day 3 but decreased on day 7. There was no significant difference in the levels of thiobarbituric acid reactive substance (TBARS) in tumor tissues between the control and cisplatin groups. The levels of TBARS in the cisplatin+PDT group were higher (47%) than those in the PDT group. Analysis of tumor tissue transcriptomes showed that the expression of genes related to the inflammatory response including CL and XCL genes increased, while that of Fn1 decreased in the cisplatin+PDT group compared with the PDT group. CONCLUSION: These results suggest that cisplatin enhances the therapeutic effect of PDT in a breast tumor-bearing mouse model. However, further clinical studies involving patients with breast cancer is needed.

FDG PET/CT to predict the curability of endoscopic resection for early gastric cancer.

PURPOSE: We evaluated the value of fluorine-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) as a complementary imaging modality to endoscopy to predict the curability of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). METHODS: The institutional review board approved this retrospective study with a waiver of informed consent. The records of patients who underwent FDG PET/CT for initial routine staging of gastric cancer from January 2012 to October 2017 were reviewed retrospectively. Among them, the patients who had EGC with well or moderately differentiated adenocarcinoma were included in this study. A total of 210 EGCs in 199 patients (mean age ± SD, 67 ± 10 years) were selected for this study. For the analysis of FDG PET/CT image, the radiotracer uptake by the primary tumor was compared with the background gastric uptake. Each case was classified as curable by ESD (no discrete radioactivity) and not curable by ESD (discrete radioactivity). RESULTS: The detection rate of EGC by FDG PET/CT was 37.1% (78 discrete radioactivity in 210 EGCs). However, for the detection of EGC that is not curable by ESD, the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve with 95% confidence intervals were 79% (67-87%), 91% (85-95%), 81% (71-88%), 89% (84-93%), and 0.85 (0.79-0.89), respectively. CONCLUSION: FDG PET/CT may be a useful complementary imaging modality to endoscopy to predict the curability of ESD for EGC.

Association between diuretics and successful discontinuation of continuous renal replacement therapy in critically ill patients with acute kidney injury.

BACKGROUND: Despite aggressive application of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI), there is no consensus on diuretic therapy when discontinuation of CRRT is attempted. The effect of diuretics on discontinuation of CRRT in critically ill patients was evaluated. METHODS: This retrospective cohort study enrolled 1176 adult patients who survived for more than 3 days after discontinuing CRRT between 2009 and 2014. Patients were categorized depending on the re-initiation of renal replacement therapy within 3 days after discontinuing CRRT or use of diuretics. Changes in urine output (UO) and renal function after discontinuing CRRT were outcomes. Predictive factors for successful discontinuation of CRRT were also analyzed. RESULTS: The CRRT discontinuation group had a shorter duration of CRRT, more frequent use of diuretics after discontinuing CRRT, and greater UO on the day before CRRT discontinuation [day minus 1 (day - 1)]. The diuretics group had greater increases in UO and serum creatinine elevation after discontinuing CRRT. In the CRRT discontinuation group, continuous infusion of furosemide tended to increase UO more effectively. Multivariable regression analysis identified high day - 1 UO and use of diuretics as significant predictors of successful discontinuation of CRRT. Day - 1 UO of 125 mL/day was the cutoff value for predicting successful discontinuation of CRRT in oliguric patients treated with diuretics following CRRT. CONCLUSIONS: Day - 1 UO and aggressive diuretic therapy were associated with successful CRRT discontinuation. Diuretic therapy may be helpful when attempting CRRT discontinuation in critically ill patients with AKI, by inducing a favorable fluid balance, especially in oliguric patients.

Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle.

Nebulin is a giant sarcomeric protein that spans along the actin filament in skeletal muscle, from the Z-disk to near the thin filament pointed end. Mutations in nebulin cause muscle weakness in nemaline myopathy patients, suggesting that nebulin plays important roles in force generation, yet little is known about nebulin's influence on thin filament structure and function. Here, we used small-angle X-ray diffraction and compared intact muscle deficient in nebulin (using a conditional nebulin-knockout, Neb cKO) with control (Ctrl) muscle. When muscles were activated, the spacing of the actin subunit repeat (27 Å) increased in both genotypes; when converted to thin filament stiffness, the obtained value was 30 pN/nm in Ctrl muscle and 10 pN/nm in Neb cKO muscle; that is, the thin filament was approximately threefold stiffer when nebulin was present. In contrast, the thick filament stiffness was not different between the genotypes. A significantly shorter left-handed (59 Å) thin filament helical pitch was found in passive and contracting Neb cKO muscles, as well as impaired tropomyosin and troponin movement. Additionally, a reduced myosin mass transfer toward the thin filament in contracting Neb cKO muscle was found, suggesting reduced cross-bridge interaction. We conclude that nebulin is critically important for physiological force levels, as it greatly stiffens the skeletal muscle thin filament and contributes to thin filament activation and cross-bridge recruitment.

Thick-Filament Extensibility in Intact Skeletal Muscle.

Myofilament extensibility is a key structural parameter for interpreting myosin cross-bridge kinetics in striated muscle. Previous studies reported much higher thick-filament extensibility at low tension than the better-known and commonly used values at high tension, but in interpreting mechanical studies of muscle, a single value for thick-filament extensibility has usually been assumed. Here, we established the complete thick-filament force-extension curve from actively contracting, intact vertebrate skeletal muscle. To access a wide range of tetanic forces, the myosin inhibitor blebbistatin was used to induce low tetanic forces in addition to the higher tensions obtained from tetanic contractions of the untreated muscle. We show that the force/extensibility curve of the thick filament is nonlinear, so assuming a single value for thick-filament extensibility at all force levels is not justified. We also show that independent of whether tension is generated passively by sarcomere stretch or actively by cross-bridges, the thick-filament extensibility is nonlinear. Myosin head periodicity, however, only changes when active tension is generated under calcium-activated conditions. The nonlinear thick-filament force-extension curve in skeletal muscle, therefore, reflects a purely passive response to either titin-based force or actomyosin-based force, and it does not include a thick-filament activation mechanism. In contrast, the transition of myosin head periodicity to an active configuration appears to only occur in response to increased active force when calcium is present.

Adjunctive Breast-Specific Gamma Imaging for Detecting Cancer in Women with Calcifications at Mammography.

BACKGROUND: Mammography detects calcium deposits sensitively, but the specificity for differentiating malignancy from benign calcifications is low. Thus, we investigated whether adjunctive breast-specific gamma imaging (BSGI) has incremental value for detecting cancer in women with suspicious calcifications detected by mammography, and compared BSGI with adjunctive ultrasonography (US). METHODS: The medical records of women without a personal history of breast cancer who underwent mammography for breast evaluation from 2009 to 2014 were reviewed retrospectively. Patients who had calcifications detected by mammography, with a result of Breast Imaging Reporting and Data System (BI-RADS) categories 3-5, underwent adjunctive US and BSGI and were included in this study. A total of 302 breast lesions in 266 women (mean age ± standard deviation 49 ± 9 years) were selected for this study. RESULTS: For detecting breast cancer using mammography plus BSGI, the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating curve with 95% confidence intervals were 94% (91-96), 90% (86-93), 91% (87-94), 94% (90-96), and 0.92 (0.89-0.95), respectively. For mammography plus US, the respective values were 97% (94-98), 51% (46-57), 68% (63-73), 94% (90-96), and 0.74 (0.70-0.78). CONCLUSIONS: Adjunctive BSGI had higher specificity than adjunctive US without loss of sensitivity. This finding suggests that adjunctive BSGI may be a useful complementary initial imaging method to improve the detection of breast cancer in women who have calcifications with suspicious morphology at mammography.