New insights in the interaction of FGF/FGFR and steroid receptor signaling in breast cancer

Luminal breast cancer (BrCa) has a favorable prognosis compared to other tumor subtypes. However, with time tumors may evolve and lead to disease progression. Thus, there is a great interest in unraveling the mechanisms that drive tumor metastasis and endocrine resistance. In this review we focused in one of the many pathways that have been involved in tumor progression, the FGF/FGFR axis. We emphasized in data obtained from in vivo experimental models since we believe that in luminal BrCa, tumor growth relies in a crosstalk with the stromal tissue. We revisited the studies that illustrate the interaction between hormone receptors and FGFR. We also highlighted the most frequent alterations found in BrCa cell lines and we provide a short review on the trials that use FGFR inhibitors in combination with endocrine therapies. The analysis of this data suggests that there are many players involved in this pathway that might be also targeted to decrease FGF signaling in addition to specific FGFR inhibitors that may be exploited to increase their efficacy.

A case report of an extremely rare type of cardiac tumor: Primary Cardiac Angiofibroma

Cardiac angiofibroma is a very rare diagnosis when a patient develops an intracardiac mass. It is a primary benign cardiac tumor with a scarcity of information in the literature. This case report illustrates a 26-year-old man with a complaint of chronic chest tightness who was firstly diagnosed with right ventricle tumor by echocardiography then underwent cardiac MRI which confirmed the presence of a highly-vascular tumor with radiologically benign behavior. Then his tumor was excised, his postoperative course was uncomplicated and he was well within almost 2 months after discharge. Ultimately the histopathologic findings demonstrated vascular and stromal tissue in favor of angiofibroma and excluded the other diagnoses with IHC and trichrome staining. Angiofibroma is a benign, highly vascular tumor, mostly discovered in the nasopharynx. When it is found in the heart, CMR and pathology are pivotal to rule in its diagnosis. It is isointense in T1 weighted and hyperintense in T2 weighted sequences with intense enhancement following contrast injection. Its pathology contains an admixture of vasculatures with CD31 positive immunoreactivity for endothelial cells and fibrotic tissue with bluish coloration in trichrome staining. Eventually, its treatment includes merely surgical excision given its benign nature.

Increase in Chymase-Positive Mast Cells in Recurrent Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma of the Parotid Gland

Incomplete excision of pleomorphic adenoma (PA) may result in recurrent pleomorphic adenoma (RPA). Furthermore, long-term neglected PA may become carcinoma ex pleomorphic adenoma (CXPA). In the present study, the relationships between mast cell-derived chymase and these tumors were examined. The tumor tissues of PA consisted of either or both glandular and fibrotic structures. Histological features of RPA were almost similar to those of PA, except that they showed multinodular structures. CXPA is composed of a mixture of PA and carcinoma. The main stromal cells in PA were myofibroblasts, whereas fibroblasts constituted the main cellular portion in the stromal tissue of RPA. Cancer-associated fibroblasts (CAFs) were present abundantly in CXPA. With increased VEGF expression, neovascularization tended to increase in RPA or CXPA. Compared with PA, chymase-positive mast cells, as well as chymase gene expression, were increased in the tumor tissues from patients with RPA or CXPA. SCF, TGFβ1, and PCNA-positive staining was widely observed in these tumor tissues. The above results suggest that mast cell-derived chymase through its direct or cooperative effects with other mediators may participate in the pathophysiology of RPA and CXPA.

A case report of an extremely rare type of cardiac tumor: Primary Cardiac Angiofibroma

Cardiac angiofibroma is a very rare diagnosis when a patient develops an intracardiac mass. It is a primary benign cardiac tumor with a scarcity of information in the literature. This case report illustrates a 26-year-old man with a complaint of chronic chest tightness who was firstly diagnosed with right ventricle tumor by echocardiography then underwent cardiac MRI which confirmed the presence of a highly-vascular tumor with radiologically benign behavior. Then his tumor was excised, his postoperative course was uncomplicated and he was well within almost 2 months after discharge. Ultimately the histopathologic findings demonstrated vascular and stromal tissue in favor of angiofibroma and excluded the other diagnoses with IHC and trichrome staining. Angiofibroma is a benign, highly vascular tumor, mostly discovered in the nasopharynx. When it is found in the heart, CMR and pathology are pivotal to rule in its diagnosis. It is isointense in T1 weighted and hyperintense in T2 weighted sequences with intense enhancement following contrast injection. Its pathology contains an admixture of vasculatures with CD31 positive immunoreactivity for endothelial cells and fibrotic tissue with bluish coloration in trichrome staining. Eventually, its treatment includes merely surgical excision given its benign nature.

First Report of Biscogniauxia mediterranea on Quercus emoryi in southern Arizona

In 2019, a decline of Quercus emoryi (Emory oak) was observed on the Coronado National Forest located in southeastern Arizona. Symptoms associated with oak mortality included crown die-back and large cankers revealing charcoal-like stromal growth. Trunks and root collars showed girdling and many affected trees also displayed evidence of gold-spotted oak borer activity. Initial surveys in stands identified clusters of severe infections. Samples with black perithecia and stromal tissue were collected from symptomatic hosts. Morphological characterization of the fungus was completed on fresh perithecial tissue. Stromata were pulvinate and black showing embedded perithecial bumps, with ostioles visible from the surface of the stroma. Asci were short stipitate and cylindrical with visible oil drops, 6.6 to 9.4 (mean: 8.8) × 139.8 to 179.9 μm (mean: 166.4). Ascospores were smooth ovoid, brown to dark brown, with narrowed and round ends, 6.9 to 9.1 (mean: 7.7) × 13.8 to 25.9 μm (mean: 16.5). Colonies grown on ½ strength potato dextrose agar (½ PDA) (Korhonen 1980) at 25°C for 14 days were whitish-grey when viewed from the top and darkened embedded spheres were visible from the bottom. Single-spored cultures were isolated by dissecting the hymenium and placing in distilled water. The suspension was streaked onto ½ PDA plates and incubated for 12 hours, and pure cultures were grown on ½ PDA. DNA was isolated from a mycelial scrape and extracted using a 10% Chelex solution (Safaee 2017). The internal transcribed spacer region was amplified with the ITS1/ITS4 primers (White et al. 1990) and PCR products were sequenced at Eurofins Scientific (Lewisville, KY). Isolates (BSS1, BSS2, BSS3, BSS4) were compared to other Biscogniauxia mediterranea sequences in the NCBI database (MG098274, EF026134) and had 100% sequence identity. Pathogenicity assays were conducted using 8-year-old Emory oaks in a greenhouse. The oaks were drought stressed and watered at 50% pot capacity for two months prior to inoculation. Each tree received approximately 2400 ml of water every two weeks for the remainder of the experiment. Eight trees were wounded three times with a 5mm corer. A 5mm plug of mycelium of isolate BSS2 was used to inoculate wounds. Four trees were used as controls and inoculated with ½ PDA plugs. Wounded and inoculated areas were assessed after three months. All eight trees exhibited dark necrotic tissue in the vascular cambium and lesions ranged from 11.4 – 25.8 mm in length and were 3.9 – 13.3 mm wide. The controls exhibited no fungal sign, lesions, or necrotic tissues. The pathogen B. mediterranea was recovered from 13 of the 24 total inoculations and its identity was confirmed with ITS sequencing. Mortality and die-back caused by Biscogniauxia spp. are commonly associated with drought-stressed trees, with increasingly hot and dry conditions routinely noted as inciting factors (Desprez Loustau et al.). Emory oaks are among the dominant tree species in much of the Madrean oak woodlands of the southwestern US and Mexico and provide vital ecological and cultural services. As southwestern states continue to experience hotter and drier, conditions, it is likely Emory oak will become increasingly susceptible to die-back and mortality due to this Biscogniauxia species (Southern et al.).

Supramolecular Host–Guest Hydrogels for Corneal Regeneration

Over 6.2 million people worldwide suffer from moderate to severe vision loss due to corneal disease. While transplantation with allogenic donor tissue is sight-restoring for many patients with corneal blindness, this treatment modality is limited by long waiting lists and high rejection rates, particularly in patients with severe tissue damage and ocular surface pathologies. Hydrogel biomaterials represent a promising alternative to donor tissue for scalable, nonimmunogenic corneal reconstruction. However, implanted hydrogel materials require invasive surgeries and do not precisely conform to tissue defects, increasing the risk of patient discomfort, infection, and visual distortions. Moreover, most hydrogel crosslinking chemistries for the in situ formation of hydrogels exhibit off-target effects such as cross-reactivity with biological structures and/or result in extractable solutes that can have an impact on wound-healing and inflammation. To address the need for cytocompatible, minimally invasive, injectable tissue substitutes, host–guest interactions have emerged as an important crosslinking strategy. This review provides an overview of host–guest hydrogels as injectable therapeutics and highlights the potential application of host–guest interactions in the design of corneal stromal tissue substitutes.

New Prospects in Neutering Male Animals Using Magnetic Nanoparticle Hyperthermia

Controlling populations of free-roaming dogs and cats poses a huge challenge worldwide. Non-surgical neutering strategies for male animals have been long pursued, but the implementation of the procedures developed has remained limited to date. As submitting the testes to high temperatures impairs spermatogenesis, the present study investigated localized application of magnetic nanoparticle hyperthermia (MNH) to the testicles as a potential non-surgical sterilization method for animals. An intratesticular injection of a magnetic fluid composed of manganese-ferrite nanoparticles functionalized with citrate was administered followed by testicle exposure to an alternate magnetic field to generate localized heat. Testicular MNH was highly effective, causing progressive seminiferous tubule degeneration followed by substitution of the parenchyma with stromal tissue and gonadal atrophy, suggesting an irreversible process with few side effects to general animal health.

Critical Analysis of Corneal Cross-linking (Part-II): Resolving the Controversial Issues (Theory versus Measurements)

Aims: To resolve the controversial issues of UV-light-initiated corneal collagen cross-linking (CXL) by theoretical formulas and measured clinical outcomes. Study Design: Analysis and measured data of CXL. Place and Duration of Study: New Vision Inc, Taipei, between June 2021 and August 2021. Methodology: The controversial issues are addressed and resolved by analytical formulas including: the validation of Bunsen Roscoe law (BRL), the cutoff light intensity, the minimum corneal thickness, the demarcation line depth, the role of oxygen and riboflavin concentration. The overall CXL efficacy is governed by UV-A light intensity, dose, exposure time, mode of exposure (pulsed or CW), the riboflavin concentration, diffusion and drops pre-operation and interoperation administration, the concentration of oxygen in the stromal tissue (pre-op and inter-op), and environmental conditions. The length of the riboflavin presoaking time and viscosity of the riboflavin film also affect the crosslink depth. Analytic formulas are derived for the scaling laws for type-I and type-II efficacy, given by the square root of light intensity, and light dose, respectively. Conclusion: The controversial issues of CXL may be partially resolved via analytic formulas, and compared with measurements. The scaling laws of type-I and type-II efficacy are different and given by analytic formulas. Our formulas also predict the maximum light intensity and the minimum corneal thickness, which are consistent with measurements.

Critical Analysis of Corneal Cross-Linking (Part-II): Resolving the Controversial Issues (Theory Versus Measurements)

To resolve the controversial issues of UV-light-initiatedcornealcollagen cross-linking (CXL) by theoretical formulas and measured clinical outcomes. The controversial issues are addressed and resolved by analytical formulas including: the validation of Bunsen Roscoe law (BRL), the cutoff light intensity, the minimum corneal thickness, the demarcation line depth, the role of oxygen riboflavin (RF) concentration. The overall CXL efficacy is governed by UV-A light intensity, dose, exposure time, mode of exposure (pulsed or CW), riboflavin concentration, diffusion and drops pre-operation and interoperation administration, concentration of oxygen in the stromal tissue (pre-op and inter-op), and environmental conditions. The length of the riboflavin presoaking time and viscosity of the riboflavin film also affect the crosslink depth. Analytic formulas are derived for the scaling laws for type-I and type-II efficacy, given by the square-root of light intensity, and light dose, respectively. The controversial issues of CXL may be partially resolved via analytic formulas, and compared with measurements. The scaling laws of type-I and type-II efficacy are different and given by analytic formulas. Our formulas also predict the maximum light intensity and the minimum corneal thickness, which are consistent with measurements.

A Histopathologic Approach to Uterine Niche: What to Expect and to Report in Hysteroscopy-Resected Isthmocele Specimens

As one of the emerging complications of caesarean sections (CSs), pathologists will have an important role in handling samples of uterine niches. An isthmocele is a defect at the site of a previous CS scar resulting in a variety of symptoms and niche-related subfertility. There is a deficiency in the literature of the histopathologic features of hysteroscopy-resected isthmocele ridges. Our aim is to fill this gap to highlight what to expect to see and what important findings to report to guide gynecologists to the results of hysteroscopic isthmoplasty in relation to symptoms improvement, fertility restoration, and potential complications. We found 22 cases of hysteroscopy-resected isthmoceles by performing a retrospective review study. The majority of the women were symptomatic with secondary infertility. The resected isthmocele edges were lined by endocervical, endometrial, and isthmic mucosa either combined or isolated depending on each case. Isthmoceles could be classified depending on the predominant lining mucosa into endocervical-isthmoendocervical (low) and endometrial-isthmic (high-intermediate) niches. This could be correlated with certain symptoms. The edges showed variably thickened fibrous and fibromuscular stromal tissue with characteristic thick-walled blood vessels. Some cases showed miscellaneous findings such as hemosiderin pigments with foreign body giant cell reaction and placental implantation site tissue reflecting a previous history of surgical repair and scar pregnancy. Cauterization artifacts may impose interpretation challenges for pathologists. Utility of certain special stains helps delineate the nature of badly cauterized tissues. It is important to report certain histologic findings in isthmocele samples to correlate with clinical findings and guide gynecologists.