Blue Cell Research Articles

Penile Ewing's Sarcoma - A Rare Entity

Abstract Introduction/Objective Ewing sarcoma is a cancer involving the bones or the tissue around bones. It is the second most common malignant bone tumour comprising 10-15% of all primary bone tumours, most commonly affecting children and young adults. It can also be seen in adults also. Males are more commonly affected then females. Any bone can be affected but the lower extremity, the pelvis, upper extremity, axial skeleton and ribs, and face cases. Similar histology tumours when seen in soft tissue are peripheral primitive neuroectodermal tumour (pPNET), neuroepithelioma, and Askin tumour. It is always difficult to know the primary site when soft tissues are involved as it can be infiltration from bone or from soft tissue to bone. Penis is least common site involved with Ewing’s sarcoma in young male. Methods/Case Report This is a case report of a 22 year old male with penile lesion. He presented with the chief complaints of mass at the shaft of penis. The partial penectomy specimen was received along with the bilateral inguinal lymph node. On gross there was a ulcero-proliferative growth. Results (if a Case Study Enter NA) On histopathological examination showed small blue round cell tumour and further immunohistochemistry with CD99 and NKX2.2 revealed the diagnosis of Ewing’s sarcoma, however lymph nodes showed reactive lymphoid hyperplasia. Conclusion The Ewing sarcoma at the penile region is rarest entity. Only 7 cases are reported worldwide. The imaging modalities like CT or MRI can be used to know the extension. The diagnosis is primarily based on morphological features, immunohistochemical analysis and translocation analysis. However it is important to find out if any other soft tissue site is involved. The important prognostic markers are presence and absence of metastasis, size of tumour, necrosis and presence of fusion transcripts.

Metastasis of a Primary Sinonasal Alveolar Rhabdomyosarcoma to the Testicle in an Adult Patient

Abstract Introduction/Objective Alveolar rhabdomyosarcoma is an aggressive tumor of skeletal muscle differentiation that predominantly affects adolescents and young adults, and is rare over 45 years of age. It has poor prognosis with metastasis, and most commonly spreads to the lymph nodes, bone marrow, and lungs. In this report, we describe a middle-aged patient with a primary sinonasal alveolar rhabdomyosarcoma which metastasized to the right testicle, an unusual metastatic site reported only a few times in literature. Methods/Case Report Our patient is a 53 year old male who presented in 2020 with recurrent epistaxis and bilateral cervical lymphadenopathy over a 2 month period. Maxillofacial CT/MRI imaging revealed a 4-cm sized mass within the left nasal cavity eroding into the ethmoid sinuses. The patient underwent endoscopic sinus surgery of the sinonasal mass, which on histology, appeared as poorly differentiated small round blue cells with numerous mitoses infiltrating as single cells and nests. These cells stained positive for vimentin, myogenin, desmin, and CD56, and negative for AE1/AE3, chromogranin, S-100, CD99, and CD45. The cells showed very high Ki67 proliferation index (70-80%) and tested positive for FOXO1 gene rearrangement, which supported the diagnosis of alveolar rhabdomyosarcoma. The patient completed chemoradiation therapy, and MRI scans over the next 2 years were negative for residual sinonasal tumor. However, the patient returned in 2022 after having undergone a right orchiectomy at an outside hospital for testicular pain, and abdominal CT showed diffuse retroperitoneal lymphadenopathy concerning for metastasis. On histology, the resected testicle showed seminiferous tubules infiltrated and destroyed by sheets of poorly differentiated small round blue cells with fibrous septae separating the nests of tumor cells into alveolar-like spaces with central loss of cohesion. The tumor cells showed the same immunohistochemical staining pattern as the primary sinonasal lesion, thus confirming it to be metastatic alveolar rhabdomyosarcoma. Results (if a Case Study enter NA) NA. Conclusion It is unusual for alveolar rhabdomyosarcomas to occur in adults over 45 years old, and is even rarer for these tumors to metastasize to the testicle. Metastases also only account for 1% of testicular tumors. Our report documents a very rare case of an alveolar rhabdomyosarcoma in a middle-aged adult which metastasized to the testicle after chemoradiation therapy.

Blue light exposure enhances oxidative stress, causes DNA damage, and induces apoptosis signaling in B16F1 melanoma cells

Studies have shown that visible light, specifically blue light, adversely affects cells, tissues, organs, and organisms. We investigated the effect of blue light on apoptosis, DNA integrity, and transcription of apoptotic and melanogenic genes using B16F1 melanoma cells. In this study, cells were irradiated with 2–50 W/m2 blue light (465 nm) for several time duration. Exposure to blue light decreased cell viability, but the pan-caspase inhibitor Z-VAD-FMK rescued blue light-induced cell death. Blue light also inhibited cell proliferation and arrested the cell cycle. Blue light-irradiated cells displayed several apoptotic features, like depolarized mitochondrial membranes and enhanced caspase-3 activity. Furthermore, blue light induced strand breaks in the genomic DNA in a dose- and time-dependent manner but did not induce the formation of cyclobutene pyrimidine dimers. The cell cycle inhibitor p21 and the pro-apoptotic gene Bax were upregulated in blue light-exposed cells, whereas the anti-apoptotic gene Bcl-2 and the apoptosis inhibitor survivin were downregulated. The key enzyme in melanin synthesis, tyrosinase, was upregulated after high-intensity (50 W/m2) blue light exposure and downregulated after low-intensity (0.2 W/m2) blue light exposure. Our study demonstrates that blue light triggers apoptosis and some of its effects are similar to those of ultraviolet radiation.

ODP272 ROUNDUP IS AN IMPORTANT DISRUPTOR THAT CAUSES PROLIFERATIVE EFFECTS ON NORMAL AND ON CANCER THYROID CELLS

Abstract Glyphosate has long be suspected to promote endocrine disruptive and even carcinogenic effects, but little is known about its effect at different concentrations on normal and on cancer thyroid cells. Since the endocrine system responds to low chemical concentrations and abnormal cells may have different sensitivity, it is essential to determine the effects of this compound at different levels, including the Acceptable Occupational Exposure Level (AOEL) and the Acceptable Daily Intake (IDA) doses. We used two human thyroid-derived cell lines strains, Nthy-ori 3-1 (from thyroid normal follicular cells) and TPC-1 (from papillary carcinoma) to test 15 different concentrations of Roundup® Original DI, ranging from 6.5 µg/L to 6.500 µg/L, including AOEL and IDA according to the Technical Note Process No. 25351. 056754/2013-17 of the National Health Surveillance Agency (ANVISA) in Brazil. Trypan blue assay and Cell Counting Kit – 8 (CCK-8) were employed to evaluate cell viability and cytotoxicity. Exposures were made for 24 and 48 hours in technical and biological triplicates. We observed a decrease in the number of viable cells at the 24h exposure compared to 48h in both strains. Exposure of Nthy-ori 3-1 and TPC-1 cells for 24h at the AOEL concentration (160µg/L) caused death of 52% and 58% of the cells, respectively, whereas IDA (830µg/L) resulted in 43% e 58% cell death. These data evidence an important disruptive effect of Roundup Original DI® at the acceptable concentrations. After 48h of exposure, AOEL and IDA concentrations caused a lower number of Nthy-ori 3-1 (19% e 15%) and TPC-1 (29% e 23%) dead cells, respectively, suggesting both thyroid strains have compensatory mechanisms that protect them from longer exposures to the herbicide. The CCK-8 assay, on the contrary, showed a proliferative effect on small concentrations: 6.5 µg/L increased the number of viable Nthy-ori 3-1 and TPC-1 cells to 113% and 118%, respectively, at 24h, and this stimulatory effect persisted after 48h of exposure. In contrast, AOEL and IDA concentrations produced a reduction in the number of both strains cells, likewise observed with the Trypan blue assay. Our data demonstrate that thyroid cells exposed to Roundup Original DI® present a non-monotone dose-response curve, which is a well-known characteristic of an endocrine disruptor. The proliferative effect produced on thyroid cells, especially TPC-1 mutant cells, by very low concentrations of this glyphosate-based herbicide widely used around the world, suggests that it may play a role in the increasing incidence rate of thyroid nodules and/or cancer that have been observed worldwide. Presentation: No date and time listed

RF19 | PSUN349 Histone Eraser and Reader Targeting Epigenetic Inhibitors Are Effective in Pancreatic Neuroendocrine Tumours

Abstract Background The 5-year survival for metastatic pancreatic neuroendocrine tumours (PNETs) is <50%, and current therapies are not effective. Thus, there is an unmet clinical need for new therapies for patients with PNETs. PNETs frequently have mutations in chromatin remodelling genes, including in Multiple Endocrine Neoplasia type 1 (MEN1), encoding menin, which is mutated in up to 40% of sporadic PNETs, and is part of multiple histone modifying complexes including the SET1/MLL methyltransferases. Aim To examine multiple classes of epigenetic inhibitors and determine which may be effective in treating PNETs. Methods BON1 and QGP1 PNET cell lines, the bronchial NET cell line H727, and the non-NET cell line HEK293T were utilised to assess >150 small molecule inhibitors targeting: histone deacetylases (HDACs); histone acetyltransferases; histone demethylases (KDMs); histone methyltransferases; bromodomain-containing proteins; menin; and DNA methyltransferases (DNMTs). MTOR inhibitors, already used clinically for PNET patients, as well as drugs targeting other tumorigenic pathways e.g. the proto-oncogene SRC, were used as comparators. Efficacy of compounds was evaluated using the Cell Titer Blue cell viability assay, and the Caspase Glo 3/7 apoptosis assay. Results At a dose of 1mM for 7 days, 26 compounds (including HDAC, KDM, bromodomain and mTOR inhibitors) significantly decreased the viability of both the BON1 and QGP1 cell lines by >50%, compared to DMSO control treated cells. Upon increasing the dose to 10mM for 7 days, 34 additional compounds, making a total of 60 compounds (including inhibitors of menin and DNMTs), decreased viability of both BON1 and QGP1 cells by >50%; and 56 and 46 compounds also reduced viability of H727 and HEK293 cells by >50%, respectively. Apoptosis assays utilising the 60 above compounds, at 10mM for 7 days, revealed that 25, 18, 14, and 9 of them could increase apoptosis by >4-fold of BON1, QGP1, H727 and HEK293 cells, respectively. Ten compounds (2 KDM, 5 HDAC and 3 bromodomain inhibitors) that were effective in reducing viability by >50% as well as increasing apoptosis by >4-fold of NET cells, were selected for further dosing (0.1-10mM) and time course investigations (3-7 days). All 10 compounds significantly reduced viability of BON1 and QGP1 cells (p<0.01) after 3 days of treatment. The KDM and HDAC inhibitors showed the greatest efficacy, by significantly (p<0.05) reducing BON1 and QGP1 cell viability at as low as 25nM treatment for 3 days. The efficacy of bromodomain inhibitors was not attained until 1000nM treatment, however these inhibitors had very little effect on the non-NET HEK293 cells. Conclusions Compounds targeting HDACs, KDMs or bromodomain-containing proteins are effective in reducing viability by >50% and increasing apoptosis by >4-fold of NET cells, and thus provide novel agents for studying anti-cancer mechanisms and potential therapeutic options for PNETs. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:12 p.m. - 1:17 p.m.

Cytomorphologic Features of Metastatic Sarcomas in Body Cavity Fluids Overlaps with Other Common Malignancies

Background: Sarcomas rarely involve body cavity fluids, accounting for less than 5% of all malignant effusions. Most existing literature describes the cytomorphologic features of sarcomas in the setting of fine-needle aspiration and/or touch preparations of targeted tissue biopsies. The objective of this study was to investigate the morphologic spectrum displayed by metastatic sarcomas in body cavity fluid specimens. Methods: The pathology database at our institution was searched for sarcoma cases involving pleural, pericardial, and peritoneal fluids between 1994 and 2019. Their clinical presentations and cytopathologic features were reviewed. Immunohistochemical (IHC) stains were performed on the cellblock sections at our institution on the DAKO Autostainer (DAKO, Carpinteria, CA). Results: Nineteen cases were identified, including 14 females and 5 males, ranging in age from 4 to 88 years old (median: 28.6 years). The body cavity sites were 11 pleural, 7 peritoneal, and 1 pericardial. There were 5 rhabdomyosarcomas, 4 osteosarcomas, 4 Ewing sarcomas, 2 endometrial stromal sarcomas, 2 leiomyosarcomas, 1 clear cell sarcoma, and 1 liposarcoma. Malignant pleural effusion was the first presentation in only 2 cases (both alveolar rhabdomyosarcomas). Three different cytomorphologic patterns were seen: 1-glandular cell pattern showing large epithelioid cells with vacuolated cytoplasm (3 cases), a 2-pleomorphic single-cell pattern showing large highly atypical cells (6 cases); 3-small round blue cell pattern showing small to intermediate-sized dyscohesive cells with high NC ratio (10 cases). Conclusion: The cytomorphologic spectrum exhibited by metastatic sarcomas in body cavity fluids often overlaps with other common malignancies such as metastatic adenocarcinomas, poorly differentiated carcinomas, and lymphomas. Keywords: Sarcoma; Cytology; Peritoneal.

Bilateral Wilms’ Tumor With Different Responses to Preoperative Chemotherapy

Wilms' tumor (WT) is a common type of primary renal tumor in the pediatric population that can equally affect both sides. Herein, we describe a case of bilateral Wilms' tumor (BWT) in a three-year-old male with different responses to preoperative chemotherapy in the two kidneys. The left kidney mass responded poorly to chemotherapy than the right kidney, which raised the suspicion of coexisting benign disease or congenital anomaly. However, it was ruled out by preoperative nuclear scan and ultrasound-guided frozen section biopsy taken from the left kidney mass. The report of a frozen section on hematoxylin and eosin (H&E) stain was positive for the small blue cell tumor. The patient was managed successfully with a total nephrectomy of the right kidney and nephron-sparing surgery (NSS) on the left kidney. The postoperative period was uneventful and was managed successfully with radiotherapy. Despite many challenges faced in the management of bilateral Wilms' tumor, surgery is the most preferable mode of therapy with chemotherapy and radiotherapy being effective in certain cases. The patient was followed up till no signs of recurrence or metastasis were observed.

The Effect of A2E on the Ca2+-PKC Signaling Pathway in Human RPE Cells Exposed to Blue Light.

Aims In a model of blue light-induced damage in N-retinylidene-N-retinylethanolamine (A2E)-loaded human retinal pigment epithelial (RPE) cells, we examined the effect of A2E on the calcium (Ca2+)-protein kinase C (PKC) signaling pathway. Methods Primary human RPE cells were cultured, and the cells in the 4th–6th passages were used in this study. The cells were divided into 5 groups: control cells (no A2E, no blue light), blue light-treated cells, blue light + chloroquine-treated cells, blue light + A2E-treated cells, and blue light + A2E + chloroquine-treated cells. The cells were first treated with chloroquine (15 μM for 12 h) and then loaded with A2E (25 μM for 2 h).The blue light intensity was 2000 ± 500 lux, and the duration was 6 h. After blue light exposure, the cells were cultured for 24 h. Fluo-3/AM staining was used to determine the level of cytoplasmic Ca2+, and the cells were photographed using a laser scanning confocal microscope to analyze the fluorescence intensity. The intracellular levels of inositol triphosphate (IP3) and diacylglycerol (DAG) were measured by enzyme-linked immunosorbent assay (ELISA). Intracellular PKC activity was measured with a nonradioactive nuclide assay. Results Among all cell groups, the levels of Ca2+, DAG, and IP3 were lowest in the control cells (P < 0.05). The Ca2+, DAG, and IP3 levels in the blue light + A2E-treated cells and blue light + chloroquine-treated cells were higher than those in the blue light-treated cells (P < 0.05). The Ca2+, DAG, and IP3 levels were highest in the blue light + A2E + chloroquine-treated group (P < 0.05). PKC activity was lowest in the control cells (P < 0.05). The PKC activity of the blue light + A2E-treated cells and blue light + chloroquine-treated cells was higher than that of the blue light-treated cells (P < 0.05), and the PKC activity of the blue light + A2E + chloroquine-treated cells was the highest (P < 0.05). Conclusion Blue light and A2E increased the levels of Ca2+, IP3, and DAG in human RPE cells and enhanced PKC activity, and blue light and A2E had a synergistic effect. Chloroquine further increased the levels of Ca2+, IP3, and DAG and PKC activity in RPE cells or A2E-loaded RPE cells exposed to blue light.

Primary intracranial extraosseous Ewing's sarcoma of the skull base in an elderly adult: illustrative case.

BACKGROUNDPrimary extraosseous intracranial Ewing’s sarcoma, also known as a peripheral primitive neuroectodermal tumor or “small round blue cell tumor,” is an extremely rare entity with limited representation in the literature beyond the pediatric population.OBSERVATIONSA 67-year-old male suffering occipital headache, nausea, and gait disturbance was found to have a large, avidly contrast-enhancing cerebellopontine angle mass extending into the cervical spinal canal with associated mass effect on medulla, cerebellum, fourth ventricle, and cervical spinal cord. This mass was not present on the imaging from 8 years prior. He underwent surgical debulking and pathology results demonstrated a malignant small round cell tumor showing diffuse immunopositivity for cytokeratins, CD99 and NKX2.2 with EWRS1-FLI1 rearrangement in 84% of the nuclei confirmatory of Ewing’s sarcoma. After 14 cycles of chemotherapy and 6 weeks of radiotherapy, 22 months after discovery, the patient remains in clinical and radiographic remission with complete return to his baseline functioning.LESSONSPrimary skull base extraosseous Ewing’s sarcoma should be considered in the differential diagnosis even in the elderly population when imaging studies demonstrate aggressive tumor growth patterns. Tumor debulking to establish a diagnosis followed by adjuvant chemoradiation therapy can result in clinical improvement with remission.

Use of gold nanoparticle-silibinin conjugates: A novel approach against lung cancer cells.

Lung cancer presents one of the most challenging carcinomas with meager 5-year survival rates (less than 20%), high metastasis and high recurrence due to chemo- and radio- resistance. An alternative or complementation to existing prognosis modalities is the use of phytochemicals such as silibinin, which targets essential cytokines, angiogenic factors and transcription factors for a profound anti-tumor effect. However, the problems of low solubility in an aqueous physiological environment, poor penetration, high metabolism and rapid systemic clearance limit the therapeutic use of silibinin. Conjugation of gold nanoparticles (GNPs) with silibinin may overcome the above challenges along with distinct advantages of biocompatibility, optical properties for monitoring and causation of cytotoxicity in cancer cells. The current study thus aims to develop silibinin conjugated gold nanoparticles (Sb-GNPs) with pH responsive release in the cancer microenvironment, optimizing several parameters for its higher activity and further evaluate the nanoplatform for their efficacy in inducing cell death in vitro against A549 lung cancer cells. GNPs was synthesized using trisodium citrate dihydrate as the reducing agent and further used for the conjugation of silibinin. The synthesized GNPs were found to be monodispersed and spherical in shape. The silibinin was successfully conjugated with gold nanoparticles and long-term stability of GNPs and Sb-GNPs nanoconjugates in suspension phase was confirmed by FTIR and DLS. Anticancer properties of Sb-GNPs were confirmed by different assay using MTT, Trypan blue dye exclusion assay and cell cycle analysis assay. After conjugation of silibinin with GNPs, the efficacy of silibinin increased 4–5 times in killing the cancer cells. This is the first report on using silibinin gold nanoconjugate system for lung cancer therapy with promising future applications.

Sulfuric acid induced-synthesis coupled with ethanol extraction-water precipitation purification method for orange fluorescent carbon dots with dual-emission: Application for methyl blue detection and cell imaging

In this work, by adjusting the sulfuric acid content in reaction solvent of ethanol, orange fluorescent carbon dots (O-FCDs) with dual-emission wavelength and blue fluorescent carbon dots (B-FCDs) with single-emission wavelength were successfully prepared using 1,3-dihydroxynaphthalene as precursor. Coupling with ethanol extraction-water precipitation purification method, pure O-FCDs and B-FCDs with yields of 9.0 % and 21.3 %, quantum yields (QYs) of 43.0 % and 13.7 % were obtained, respectively. The structures and optical properties of O-FCDs and B-FCDs were investigated by TEM, AFM, Raman, FT-IR, XPS, UV–vis, fluorescence analysis etc. The results revealed that sulfuric acid promoted the carbonization and the oxidation of precursor in the reaction process. In comparison with the B-FCDs, O-FCDs showed narrower lattice spacing and band gap, demonstrating the important role of sulfur-doping in fluorescence tuning. Additionally, O-FCDs showed good sensitivity for methyl blue with a linear response range of 0.05–100 μM (LOD was 20 nM) and the satisfactory results were obtained when O-FCDs were applied to the detection of methyl blue in real fish sample. Moreover, two FCDs showed good biocompatibility and negligible cytotoxicity proved by MTT experiment, while, O-FCDs showed better cell imaging effects than that of B-FCDs. Therefore, the O-FCDs had a broad application prospect as sensing platform in detection of methyl blue and for imaging in biological field.

Potassium-enriched graphite for use as stable hybrid anodes in high-efficiency potassium batteries

Potassium-ion batteries (PIBs) have attracted significant attention due to their low cost and high energy density. Despite being a promising anode candidate for PIBs, graphite is still plagued by limited capacity and fast capacity degradation with low coulombic efficiency (CE). Herein, we propose a high-capacity and highly stable potassium-enriched graphite (KRG) anode which surpasses the limitation of parent graphite. The KRG is characteristic of possessing the potassium-graphite intercalation compounds as a potassiophilic host for uniform and high-efficiency plating/stripping of potassium metal. The robust mixed conducting network possessed by the KRG is beneficial for mitigating drastic volume change of the electrode and improving ion/electron transport. A specific capacity of ∼520 mAh/g was demonstrated for KRG anode as the optimized value to maximize the capacity storage while suppressing dendrites growth. With a stable solid-electrolyte interphase buildup, the KRG/Prussian blue full cell with a controlled anode/cathode capacity ratio of 1.1:1 can deliver a high capacity of 108 mAh/g with a CE of 99% after 180 cycles at 1C. Our results provide valuable insights into the rational design of graphitic anodes for high-energy-density PIBs.

Simulation of a cholesteric blue phase cell with large but finite thickness

We investigate the structure of a cholesteric blue phase (BP) liquid crystal cell of finite thickness under an electric field normal to the planar surfaces confining the liquid crystal. We carry out large scale simulations to consider cases in which the thickness of the BP liquid crystal is approximately 40 times the BP lattice constant (typical thickness in experiments), larger than that of previous simulation studies. Our calculations clearly demonstrate that the number of periodic structures along the thickness direction (thickness divided by the lattice constant) is discretized by the presence of confining surfaces. The stability of the so-called BP X structure over the BP I under the electric field, as well as the electrostriction, is confirmed. The metastability of the BP X structure after the cessation of the electric field, demonstrated in a recent experiment [Nat. Mater. 19, 94 (2020)] is also shown. We also perform calculations for the reflection spectra of the BP structures, and clearly observe the shift of the reflection peak due to electrostriction. Our study demonstrates the role of finite thickness on the behavior of a BP cell.

Intercalation-deposition mechanism induced by aligned carbon fiber toward dendrite-free metallic potassium batteries

Metallic potassium (K) anodes are highly desirable for high energy density batteries. However, challenges lie in uncontrollable dendrite growth and/or inevitable generation of dead K. Here, composite anodes are constructed by covering a layer of aligned carbon fiber on the surface of each metallic K anode (K-ACF). Symmetrical K-ACF//K-ACF cells can work stably without short circuit for over 600 h, which is quite longer than cells using composite anodes with unaligned carbon fiber (K-UCF) and bare metallic K anodes. Comprehensive characterizations reveal a stepwise intercalation-deposition process on the K-ACF anode during the K plating, and the intercalation is proved to be necessary for the uniform K+ flux due to the improved potassiophility of potassiated ACF. Besides, the aligned structure of ACF offers a uniform current density and K+ ion flux on the surface of composite anodes, promoting the stable K stripping/plating. The K-ACF//Prussian blue (PB) cell exhibits a high discharge capacity of 83.6 mAh g−1 (267.4 Wh kg−1 based on the mass of PB) under a charge/discharge rate of 200 mA g−1 with a capacity loss rate of 0.044% per cycle. This work opens up a new avenue toward high energy and dendrite-free potassium batteries.

S1998 Colonic Merkel Cell Carcinoma of Unknown Primary: Small Cell Carcinoma Outside the Usual

Introduction: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin carcinoma with documented metastases to the liver, lungs, and gastrointestinal (GI) tract. Colonic metastases are rare but seen with recurrent or primary cutaneous lesions. Described is a patient who presented with bowel obstruction with a hepatic flexure MCC of unknown primary (MCCUP). Case Description/Methods: A 69-year-old female with a history of breast, lung, and anal cancer presented to the emergency department with abdominal pain and distension. Computed tomography of her abdomen demonstrated dilated loops of small bowel and a partial obstruction with transition point in the hepatic flexure. Colonoscopy demonstrated a 4 cm mass at the hepatic flexure obstructing the lumen. Biopsy revealed a high-grade neuroendocrine carcinoma. A right colectomy and histopathology confirmed small cell neuroendocrine carcinoma involving the colonic wall into the pericolic adipose tissue with nodal involvement. It was positive on cytokeratin CAM 5.2, synaptophysin, and Merkel cell polyomavirus (MCPvY) and negative on CDX-2 and TTF-1, excluding primary bowel or lung small cell carcinomas, respectively. Dermatologic evaluation did not reveal a primary cutaneous lesion. Genetic testing was unremarkable. Discussion: This is the first case of MCCUP presenting with colonic obstruction; prior described cases of MCC metastatic to the colon were recurrent disease or from primary skin lesions. Because MCC is rare, has non-specific symptoms, and may lack a primary lesion, MCCUP must be distinguished from other small round blue cell malignancies more commonly found in the GI tract. Thus, neuroendocrine, keratin and MCPyV ancillary staining are critical to distinguish MCC from B-cell lymphoma, small cell carcinoma of bowel or lung primary, and other metastatic dermal malignancies. MCPyV testing in the absence of prior diagnosis is uncommon but vital to the workup of neuroendocrine carcinomas when CDX-2 and TTF-1 are negative as MCPyV positive lymph nodes predict worse outcomes such as disease-free survival. In this patient immunosuppression and prior radiation increased the risk of MCC, and even suggest that this might be a colonic primary. Rarely, MCC and MCCUP are root causes of neuroendocrine carcinomas of the GI tract. In immunocompromised patients, biopsy and pathologic staining are necessary to distinguish insidious malignancies. MCPyV analysis is helpful for diagnosing MCCUP and informing its prognosis.

IL-9 neutralizing antibody suppresses allergic inflammation in ovalbumin-induced allergic rhinitis mouse model.

Allergic rhinitis is mainly mediated by IgE after specific individuals are exposed to allergens. It is a common nasal mucosa disease of non-infectious chronic inflammatory disease and is often accompanied by asthma and conjunctivitis. In the study of allergic asthma, it was found that IL-9 participates in the pathogenic development of asthma. Because asthma and allergic rhinitis have the same airway and the same disease, it is inferred that IL-9 may also play an important role in allergic rhinitis. BALB/c mice received intranasal stimulation of ovalbumin (OVA) treatment at different times. The nasal mucosa of the mice were then sliced and stained with Sirius red and Toluidine blue, and eosinophils and mast cells in the mucosa were counted. ELISA was used to detect the expression of OVA-IgE in peripheral blood. The Th2 cell fraction in the mouse spleen was detected by flow cytometry. The expressions of IL-4, IL-5, IL-9, and IL-13 and their mRNA in mucosa were detected by real-time PCR and flow cytometry bead array analysis. Finally, the expression changes of Thymic stromal lymphopoietin related proteins and its mRNA, JAK1/2, and STAT5 proteins were detected by real-time PCR and Western blot. After the intervention with the IL-9 neutralizing antibody, the symptoms of allergic rhinitis in mice were significantly reduced. The expression of OVA-IgE in the peripheral blood of mice was inhibited, the fraction of Th2 cells in the spleen decreased, the related cytokines (IL-4, IL-5, and IL-13) were inhibited, and their functions decreased. The TSLP-OX40/OX40L signal pathway and JAK1/2-STAT5 signal are inhibited. IL-9 neutralizing antibody has a good therapeutic effect on the mouse model of allergic rhinitis, which may be related to the TSLP-OX40/OX40L pathway and JAK1/2-STAT5 signaling.

Aloe vera and ofloxacin incorporated chitosan hydrogels show antibacterial activity, stimulate angiogenesis and accelerate wound healing in full thickness rat model.

Burns are potentially fatal and physically debilitating injuries, causing psychological and physical scars and result in chronic disabilities. A well vascularized wound bed is required to achieve complete and scar free wound closure. For many centuries, a variety of herbal plants have been used for wound healing, among these aloe vera (AV) has been found to be very effective in wound healing. Secondly, the main reason for delayed wound healing is bacterial infections. Ofloxacin (OX) has been reported as an active antibacterial drug for topical infections and it is effective against both positive and negative bacterial strains. In current research three different concentrations of OX (0.5, 2.5, and 5mg) were loaded into chitosan (CS)/AV based hydrogels prepared by freeze gelation. The surface morphology of prepared CS/AV based OX loaded hydrogels were evaluated by scanning electron microscopy (SEM). In drug release analysis, 0.5mg OX loaded hydrogel showed a sustained drug release behavior over 3 days period. An effective dose dependent antibacterial activity was exhibited by OX loaded hydrogels. Alamar Blue cells viability assay revealed that 0.5mg OX hydrogel (CA 0.5 OX) showed comparatively better 3T3 fibroblast cells proliferation as compared to CA 2.5 OX (2.5mg OX) and CA 5 OX hydrogel (5mg OX). Moreover, all OX loaded hydrogels showed good angiogenic activity in CAM bioassay while higher angiogenic potential was observed from CA 0.5 OX containing comparatively lower concentration of OX. These OX incorporated CS/AV based hydrogels are promising wound dressings for future clinical use.

Primary Bilateral Ovarian Lymphoma: A Rare Case Report

Primary ovarian lymphomas constitute 0.5% of all ovarian malignancies. We report one such case in a middle-aged woman who presented with a bilateral ovarian tumor. Bilateral oophorectomy with salpingectomy was sent for frozen section analysis that revealed a round cell tumor. Final histopathology showed a mitotically active small round blue cell tumor arranged in diffuse sheets and chords with an evident starry-sky pattern. Extensive immunohistochemistry (IHC) panel was performed. Histopathology along with IHC did not classify the tumor into diffuse-large-B cell-lymphoma or Burkitt lymphoma and a final diagnosis of high-grade B cell lymphoma (HGBL) was made. This case is presented for its rarity and to discuss the challenges on IHC to subclassify a lymphoma as HGBL. Although rare, the possibility of primary ovarian non-Hodgkin lymphoma should be kept in mind when dealing with bilateral ovarian tumors as a timely and accurate diagnosis can save unnecessary surgeries and improve outcome.

Construction and characterization of organic photovoltaic cells sensitized by Chrysanthemum based natural dye

In this work, natural dyes from three different species of the same flower family (Chrysanthemum), which containing anthocyanin were extracted and properly prepared to be used as photosensitizers in DSSCs construction. The cells were fabricated with titanium dioxide nanoparticles (TiO2) for the photoanodes, whereas platinum electrodes were used for the photocathodes. To understand the behavior of light absorption in addition to the coloring components present in the dyes and the molecular functional groups present in the samples, the UV–Vis absorption spectroscopy and FTIR spectroscopy were used respectively. The performance and efficiency of solar cells were evaluated to establish the photovoltaic criteria for each DSSC built. Through electrochemical characterizations, it was possible to notice that the highest photovoltaic conversion efficiency was obtained with the Chrysanthemum Violet (CV) cell, with efficiency (η) of 1.348%, compared to 1.229% and 0.485% for the Chrysanthemum Green (CG) and Chrysanthemum Blue (CB) cells, respectively. The CV cell also has the highest open circuit voltage (VOC) at 0.58 V. The results corroborate to present the organic solar cells as a viable option for the electric energy generation.

NON-HODGKIN'S LYMPHOMA VERSUS TOOTH ABSCESS: IMPORTANCE AND CHALLENGES OF A CORRECT DIAGNOSIS

A 41-year-old male patient reported pain and discomfort in the jaw for 2 months. A private dentist established the diagnosis of a tooth abscess and prescribed antibiotics for 2 weeks. On extraoral exam, slight facial asymmetry and an enlarged and firm right submandibular lymph node were noted. On intraoral exam, a lobulated, reddish, partially ulcerated, soft, and asymptomatic nodule in the maxillary ridge referring to tooth 16, measuring 2.5 cm, was observed. A differential diagnosis of lymphoma and fibrosarcoma was established, and an incisional biopsy was performed. Histopathologic examination revealed a proliferation of round and blue cells, compatible with lymphoma. The complementary immunohistochemical examination was positive for CD20 and BCL6. Dentists should consider lymphoma as a diagnostic hypothesis among lesions that grow rapidly and cause diffuse bone resorption. To avoid iatrogenesis and improper drug prescriptions, dentists should always make detailed anamnesis and complete physical examinations of patients. A 41-year-old male patient reported pain and discomfort in the jaw for 2 months. A private dentist established the diagnosis of a tooth abscess and prescribed antibiotics for 2 weeks. On extraoral exam, slight facial asymmetry and an enlarged and firm right submandibular lymph node were noted. On intraoral exam, a lobulated, reddish, partially ulcerated, soft, and asymptomatic nodule in the maxillary ridge referring to tooth 16, measuring 2.5 cm, was observed. A differential diagnosis of lymphoma and fibrosarcoma was established, and an incisional biopsy was performed. Histopathologic examination revealed a proliferation of round and blue cells, compatible with lymphoma. The complementary immunohistochemical examination was positive for CD20 and BCL6. Dentists should consider lymphoma as a diagnostic hypothesis among lesions that grow rapidly and cause diffuse bone resorption. To avoid iatrogenesis and improper drug prescriptions, dentists should always make detailed anamnesis and complete physical examinations of patients.