Posterior Flank Research Articles

A new species of the Amolops monticola group (Anura, Ranidae) from southern Yunnan, China

A new species of the Amolops monticola group is described from Yunnan Huanglianshan National Nature Reserve, southern Yunnan, China. Morphologically, the new species is characterized by a moderate body size (snout–vent length 38.3–40.8 mm in adult males and 62.3–63.1 mm in adult females), head being longer than wide, nostril to snout tip distance being slightly smaller than eye to nostril distance, the presence of pineal body, distinct tympanum, vomerine teeth being invisible in males and weak but visible in females, distinct dorsolateral folds, the absence of outer metatarsal tubercle, the presence of vocal sac and nuptial pad in adult males, dorsal surface of head and body being green with no or a few black dots, and the presence of a few large flat white tubercles on the posterior inferior flank. Genetically, the uncorrected genetic distance between the new species and other species of the A. monticola group ranged from 3.0% to 7.6% in 16S ribosomal RNA and from 7.2% to 17.1% in NADH dehydrogenase subunit 2 gene sequences. Currently, the new species is known only from its type locality in Lvchun County, Honghe Prefecture, Yunnan Province, China.

387 Pathogenicity of a CCDC6-RET Fusion in Malignant Peripheral Nerve Sheath Tumor (MPNST)

OBJECTIVES/GOALS: RETgene fusions in sarcoma are rare and their impact on pathogenicity is unknown. Malignant peripheral nerve sheath tumors (MPNST) are a deadly, genomically heterogenous soft tissue sarcoma rarely harboring targetable aberrations. We present a case of a CCDC6-RET fusion MPNST sensitive to RET-inhibitor therapy in a xenograft model. METHODS/STUDY POPULATION: Lung tumor tissue was obtained per an approved collection protocol from a 21yo male patient with a spontaneous MPNST harboring an inactivating mutation in NF-1 and a CCDC6-RET gene fusion detected by a commercially available sequencing panel (Signatera). To confirm pathogenicity of the RET fusion, fresh tumor tissue was engrafted into immunocompromised NSG mice in the anterior and posterior flanks, harvested at ~10 weeks, and re-transplanted into bilateral flanks. When tumor diameters reached 0.5-1cm (~4 weeks), mice were randomized into 3 groups (n=6/group) and treated with either vehicle (V) (PBS), the RET-specific inhibitor selpercatinib (S) (20mg/kg twice daily), or the multi-kinase inhibitor cabozantinib (C) (30mg/kg daily) by oral gavage. Mice were monitored weekly for weight and tumor size. RESULTS/ANTICIPATED RESULTS: 92% (33/36) of implanted tumors were evaluable for treatment response. Pre-treatment tumor volumes (mm3) across all three groups were similar (mean/Std Dev – V: 230/111, S: 271/132, C: 230/123). At day 7, tumor growth was significantly inhibited by S and C versus V (ANOVA p < 0.001, post-hoc Tukey’s V vs S p= 0.0178, V vs C p< 0.0001, S vs C p= 0.0005). V-treated tumors increased in volume by 60% while S reduced tumor volume by ~80% and C reduced tumor volume by ~20%. S and C treatments were tolerated well. and S improved survival with 100% of mice alive at day 63 vs 0% in V and C groups. 6 of the 12 implanted tumors treated with S, 50% increased in size after ~6-weeks following a >90% initial tumor reduction in tumor volume. Follow-on molecular studies in S-resistant tumors are ongoing. DISCUSSION/SIGNIFICANCE: Targetable genomic changes in MPNST, especially in RET, are infrequent and often considered stochastic. Our findings suggest that precision medicine approaches pairing genomic sequencing and in vivotesting of target gene pathogenicity may guide treatment planning and novel discovery for rare, difficult to treat sarcomas.

Dietary lipids management: are there any benefits from the prevention and treatment of 4T1 murine breast carcinoma?

This study investigated the effect of vegetable and fish oils with different n-3 / n-6 PUFAS ratios on the lipoprotein profile and on the development of murine breast cancer 4T1. Female Balb/c mice (6-7 weeks) received diets containing 4.0% fat during seven weeks. On the fourth week, animals were inoculated into the posterior left flank with 2.5 × 106 4T1 cells. Body weight and food intake were registered and the profile serum lipoproteins was determined. Tumor volume, histopathological and immunohistochemical studies, myeloperoxidase and N-acetylglucosaminidase activities, TNF-α, hemoglobin and VEGF levels were analysed. The highest n-3 / n-6 ratio was found in fish oil (15.8:1), followed by linseed (2.4:1), canola (1:2.1) and soybean (1:9.4) oils. Body weight, food and caloric intake, lipoprotein profile, tumor weight, tumor evolution and histopathological analysis were not different. Canola oil increased cell proliferation when compared to soybean oil, and fish oil changed the inflammatory response and increased VEGF in tumors compared to other groups. The type of fatty acid and the high ratio of n-3 / n-6 PUFAs in the diet influenced cell proliferation and inflammation in the tumor differentially, highlighting the increase of neutrophils and VEGF levels in animals fed on fish oil.

Almost slipped through the crack: Pediatric patient with bilateral slipped rib syndrome and twelfth rib syndrome of the eleventh ribs

Slipped rib syndrome is a rare disorder in which there is hypermobility of the anterior false ribs, resulting in the tips of the ribs moving or slipping under the superior rib. Alternatively, twelfth rib syndrome is caused by irritation of the twelfth intercostal nerve related to the hypermobility of the twelfth rib. In this report, we present a case of a 15-year-old male who presented with debilitating pain in the left posterior flank that persisted despite multiple medications and physical therapy. He was diagnosed with left-sided slipped rib syndrome and twelfth rib syndrome of the eleventh rib which was treated with eleventh rib excision. Less than one year later he developed right-sided pain and was ultimately diagnosed with right-sided slipped rib syndrome and twelfth rib syndrome of the eleventh rib for which he underwent right ninth and tenth costal cartilage excision and right eleventh rib excision. The patient then had complete resolution of his pain. A delineation between slipped rib syndrome and twelfth rib syndrome is important since they are both relatively rare and often misdiagnosed. Our case report is significant since our patient had both of these rare diseases bilaterally which to our knowledge has not been previously published. • Slipped rib syndrome and twelfth rib syndrome are rare causes of chest and back pain. • Increased awareness will decrease unnecessary studies and pain for these patients. • Our patient had bilateral SRS and twelfth rib syndrome, which has not been not previously described. • Resection of the affected rib with cryoablation of the intercostal nerve is a safe and effective treatment.

Chemopreventive role of Tin oxide-Chitosan-Polyethylene glycol-Crocin nanocomposites against Lung cancer: An in vitro and in vivo approach

BackgroundLung cancer (LC) is a foremost cause of cancer-associated mortalities worldwide and it causes 17 % of the total cancer incidences and 20 % of the cancer-associated mortalities annually. ObjectiveIn this exploration, we intended to formulate the Tin oxide-Chitosan-Polyethylene glycol-Crocin nanocomposites (SCP-Cr-NCs) and examine its anticancer role against the LC in both in vitro and in vivo models. MethodologyThe formulated SCP-Cr-NCs were characterized using several methods. The LC was initiated to the BALB/c mice via injecting the 2 × 106 of A549 cells into the posterior flank and treated with the 10 and 20 µM of formulated SCP-Cr-NCs for 19 days. The tumor weight and xenobiotic dysfunction markers status was examined by standard methods. The status of pro-inflammatory markers was studied using ELISA kits. The lung histology was examined microscopically. The viability of SCP-Cr-NCs treated A549 cells were investigated. The ROS and MMP status and apoptosis in the SCP-Cr-NCs treated A549 cells were inspected by fluorescence staining techniques. ResultsThe tumor weight and the status of xenobiotic dysfunction markers were remarkably reduced by the SCP-Cr-NCs. The SCP-Cr-NCs supplementation also diminished the IL-1β, TNF-α, IL-6, and CEA. The viability of SCP-Cr-NCs administered A549 cells were reduced drastically. The outcomes of fluorescence assay was demonstrated that the SCP-Cr-NCs were diminished the MMP and elevated the ROS status and apoptosis in the A549 cells. SCP-Cr-NCs also restrained the cell adhesion of A549 cells. ConclusionCollectively, our findings provided the evidence that the formulated SCP-Cr-NCs demonstrated the anticancer potential and it could be a talented chemopreventive candidate to treat the LC.

Decreased expression of ATF-3 in melanoma promotes tumor growth via ERK and AKT pathways

<h3>Introduction</h3> Activating transcription factor 3 (ATF-3), a cyclic AMP-dependent transcription factor that is encoded by the ATF-3 gene, plays a regulatory role in melanoma, although its function during tumor progression is unknown. Here we evaluated ATF-3 expression during melanoma evolution to elucidate its role in melanogenesis. <h3>Materials and Methods</h3> Primary and metastatic melanoma cell lines, patient melanomas and murine melanoma xenografts were evaluated by immunofluorescence, Western Blot and RT-PCR studies. Melanoma cell lines were retrovirally transfected with ATF-3 overexpressing vectors and CCK8, wound healing and Matrigel invasion studies were performed to test for proliferation, migration and invasive properties, respectively. Xenograft murine models were designed by subcutaneously injecting melanoma cells or its overexpressed counterpart into the anterior and posterior flanks of nude mice to evaluate tumor size and rate of formation. <h3>Results</h3> By immunofluorescence, ATF-3 staining declined in metastatic versus primary melanoma cell lines and with progression from patient nevi to primary to metastatic melanomas. Analysis of TCGA skin cutaneous melanoma database showed that lower ATF3 expression correlated with poor prognosis. Metastatic melanoma cell lines with retrovirally-induced ATF-3 overexpression (A2058 and C8161 ATF-3 OE) exhibited decreased prolif- eration, migration and invasion. GO and KEGG analyses of our RNA seq data showed downregulation of phospho- rylated ERK and AKT in A2058 ATF-3 OE cells that was further validated by Western Blot. In vivo, xenografted A2058 ATF-3 OE cells formed smaller and less abundant tumors in murine subcutis than did control cells, and Ki-67 staining confirmed lower labeling indices in ATF-3 overexpressing lesions. <h3>Conclusions</h3> ATF-3 expression is associated with melanoma virulence and thus provides a potential target for novel therapies and predictive biomarker applications.

Short Communication: Presence of the vulnerable freshwater goby Sicyopus auxilimentus (Gobiidae, Sicydiinae) on Sangihe Island, Indonesia

Abstract. Hasan V, Valen FS, Islamy RA, Widodo MS, Saptadjaja AM, Islam I. 2021. Short Communication: Presence of the vulnerable freshwater goby Sicyopus auxilimentus (Gobiidae, Sicydiinae) on Sangihe Island, Indonesia. Biodiversitas 22: 571-579. A single specimen of freshwater goby Sicyopus auxilimentus was photographed and collected using fish traps between 8 and 15 September 2019 in the Laine waterfall, Sangihe island district, North Sulawesi Province, Indonesia. S. auxilimentus is amphidromous that live in both freshwater and marine environments. This species is currently listed as Vulnerable (VU) within the IUCN Red List Status. The specimen was identified as male S. auxilimentus based on the coloration of the preserved specimen: background yellowish; scale edges brown; posterior flanks and caudal peduncle orange; first dorsal fin black, second dorsal fin dusky black; pectoral fin slightly brown; ventral fin slightly dusky; anal fin blackish; caudal fin dusky brown. Specific morphological features were as follows: the base of the first dorsal fin was not connected to the second dorsal fin base; distance between the base of first and second dorsal fin was generally less than half of eye diameter; ventral fin rays were fused to belly only between fifth rays; posterior margin of caudal fins rays was rounded; scales were all ctenoid; scales appeared on the caudal peduncle, and between anal and second dorsal fins; anterior to which, scales became widely spaced and did not imbricate. Meristic characters were as follows: first dorsal fin rays VI; second dorsal fin rays I+9; ventral fin rays I+5; pectoral-fin rays 14; anal-fin rays I+9; caudal-fin rays 13; scales in lateral series 13; scales in zigzag series 7; scales in transverse series backward 7; scales in transerves series forward 4. This finding is considered the first record in Sulawesi and the fifth from Indonesian waters after findings in Halmahera, Java, Bali and Lombok. This record enhances the understanding of the distribution of S. auxilimentus in Indonesian waters. Monitoring is needed to assess the possibility of Sangihe Island being a growth ground, spawning ground, and/or on the migration route of S. auxilimentus. In the Laine waterfall, Sangihe island, freshwater conditions were as follows: salinity 3.5 psu, temperature 23-25°C, and dissolved oxygen 7.7-9.2 mg/l, which were ideal habitat for S. auxilimentus. S. auxilimentus from Sangihe Island, had 0.000 genetic distance than from S. auxilimentus from Bali, while the next closest genetic distance was S. zosterophorus at genetic distance of 0.090. In addition to onsite conservation, domestication programs are needed to increase commercial availability without depending on natural catches.

Perforator Dissection Simulation: A High-Fidelity Five-Flap Porcine Training Model.

Perforator dissection can be technically demanding with a steep learning curve. Inadvertent perforator damage during dissection can be minimized with practice and familiarity with tissue-handling techniques unique to perforator dissection. There currently lacks a simulation model that mimics the human perforator in size and course. We present a porcine training model with five consistent perforator flaps per side that can be readily harvested and is a reproducible simulation model. Five fresh cadaveric pigs were used in this study to evaluate the feasibility and location of the perforators. Ten perforators were dissected out in each pig (five per side) by the same surgeon. The length of perforator was measured and intramuscular route was noted. The ease of dissection was graded, and its similarity to actual surgery was graded as well. Five consistent perforators were identified across each side of five fresh cadaveric pigs. The perforators were located, namely in the neck, anterior flank, posterior flank, rectus and hindlimb. They were fasciocutaneous and had an intramuscular course of each (average 2.5cm length). The perforators were found to be on each side of the pig, giving ten perforators for dissection practice in total. The five perforators named in this porcine model are easily replicated and can be performed for perforator dissection simulation and practice.

Description of a new species of Pseudophilautus (Amphibia: Rhacophoridae) from southern Sri Lanka

We describe a new Pseudophilautus species, P. conniffae sp. nov. from southern Sri Lanka. It was previously confused with Pseudophilautus rus (Manamendra-Arachchi &amp; Pethiyagoda). The new species differs from the latter by the combination of the following characters: fourth toe webbing to penultimate subarticular tubercle on inner and outer sides (vs. fourth toe webbing in between penultimate and anetpenultimate subarticular tubercles on inner and outer sides), presence of conical median lingual process (vs. absent), and black patches on the posterior flank, anterior and posterior edges of the thigh (vs. black patches on the anterior surface of the thigh). Pseudophilautus conniffae sp. nov. may be sympatric with P. limbus (Manamendra-Arachchi &amp; Pethiyagoda), which shares certain characters with the new species. The new species is, however, distinguished from P. limbus by the following characters: having supernumerary tubercles on manus (vs. lacking), absence of frontoparietal ridges (vs. presence), fourth toe webbing to penultimate subarticular tubercle on both sides (vs. fourth toe webbing between penultimate and anetpenultimate subarticular tubercle on both sides), third toe webbing to distal subarticular tubercle on both sides (vs. distal subarticular tubercle on outer side and below penultimate subarticular tubercle on inner side), and having the dorsum light brown with dark brown patches (vs. black and yellow variegated pattern on dorsum). The new species may be restricted to the southwestern wet zone of Sri Lanka. It is compared with all known Pseudophilautus species and also provided with a field key to identify it from those species that are sympatric with it or inhabit the southwestern wet zone.

Etmopterus marshae sp. nov, a new lanternshark (Squaliformes: Etmopteridae) from the Philippine Islands, with a revised key to the Etmopterus lucifer clade.

A new species of lanternshark, Etmopterus marshae (Squaliformes: Etmopteridae), is described from the Philippine Islands, western North Pacific Ocean. The new species occurs along insular slopes at a depth range of 322-337 m. The new species resembles other members of the "Etmopterus lucifer" clade in having linear rows of dermal denticles, and most closely resembles E. burgessi from Taiwan and E. evansi and E. pycnolepis from the South Pacific. It can be distinguished from all other members of the E. lucifer clade by a combination of characteristics, including length of anterior and posterior flank branches being of relatively equal length, straight vs. curved anterior flank marking, relative lengths of caudal markings, coloration, and relatively small size. A revised key to the revised key to the Etmopterus lucifer clade is provided.

Clinical outcomes of children with Wilms tumor treated on a SIOP WT 2001 protocol in a tertiary care hospital in south India

Wilms tumor is the most common pediatric renal malignancy. While developed countries have had excellent survival, it remains poorer by comparison in developing countries. The aim was to analyze the clinical outcome of children with Wilms tumor managed in a developing country from 2004 to 2014 by the SIOP WT 2001 protocol. Fifty-nine children with Wilms tumor managed by a SIOP WT 2001 regimen from 2004 to 2014 were analyzed. The median age at presentation was 36 months, and 59% were boys. The average size of the tumor at presentation was 523mL. Inferior vena cava thrombus was present in 11, distant metastases in 18, and bilateral tumors in six. Preoperative chemotherapy was given to all children after a diagnostic core needle biopsy. Preoperative chemotherapy reduced the tumor size to a mean of 208mL and resolved venacaval thrombus in eight. Fifty-five children underwent definitive surgery while two children died during preoperative chemotherapy and two remained inoperable. All surviving children received adjuvant chemotherapy with 17 receiving radiotherapy as well. The overall survival (OS) was 80% and the event-free survival (EFS) was 73% after a mean follow up of 42 months after completion of therapy. The tumor volumes at presentation and the incidence of venous tumor thrombosis in our cohort were much higher than those reported from developed countries. The incidence of metastatic disease at diagnosis (30.5%) was significantly higher than the 10-12% reported in Western data, but similar to that reported from various developing countries (14.1-31%). The OS in our cohort was 80% and the EFS was 73% with there being no events after 28 months. Although the survival rate for localized disease is similar to that in developed countries, the OS for metastatic disease was significantly less (50% vs. 75%). We also found that using an upfront posterior flank core biopsy was safe and beneficial for differentiating Wilms tumor from other pediatric renal tumors that are less chemosensitive. In a resource-restricted environment such as ours, the SIOP WT 2001 protocol has been found to show excellent results.

Use of Pretherapy Core Biopsy in the Diagnosis of Pediatric Renal Tumors.

Background:Pretreatment core biopsy of pediatric renal tumors has been advocated by United Kingdom Children's Cancer Study Group to circumvent the disadvantage of International Society of Paediatric Oncology protocol, where neoadjuvant chemotherapy initiated without histopathological confirmation can result in over- or under-treatment.Aim:This study aims (a) to assess if pretherapy core biopsy correlates with the nephrectomy biopsy; (b) to assess if neoadjuvant chemotherapy changes Wilms tumor (WT) histology, and (c) to assess the incidence of biopsy site recurrence.Materials and Methods:Seventy-six children from 2005 to 2016 with renal tumors who underwent a pretherapy core biopsy were included in the study. The biopsy was performed through the posterior flank post-ultrasound marking of the renal mass, by administering intravenous anesthesia.Results:Of the 62 children with WT, an accurate diagnosis was possible in 61. Accurate prediction of anaplasia was possible only in 25%. Reduction in blastemal elements was seen in 26 patients with 10 of them showing completely necrotic tumor. Eleven of the 14 children with non-WT were accurately diagnosed. Core biopsy corroborated with the nephrectomy biopsy in all but 4 patients. Two specimens were inadequate and two cases of congenital mesoblastic nephroma were inaccurately diagnosed, one as spindle cell neoplasm and the other as WT. Biopsy site recurrence was seen in 1 child.Conclusion:Pretreatment posterior flank core biopsy in the diagnosis of pediatric renal tumors is safe, simple, and cost-effective with minimal complications.

Stab injury to the preauricular region with laceration of the external carotid artery without involvement of the facial nerve: a case report

BackgroundOpen injuries to the face involving the external carotid artery are uncommon. These injuries are normally associated with laceration of the facial nerve because this nerve is more superficial than the external carotid artery. Hence, external carotid artery lesions are usually associated with facial nerve dysfunction. We present an unusual case report in which the patient had an injury to this artery with no facial nerve compromise.Case presentationA 25-year-old Portuguese man sustained a stab wound injury to his right preauricular region with a broken glass. Immediate profuse bleeding ensued. Provisory tamponade of the wound was achieved at the place of aggression by two off-duty doctors. He was initially transferred to a district hospital, where a large arterial bleeding was observed and a temporary compressive dressing was applied. Subsequently, the patient was transferred to a tertiary hospital. At admission in the emergency room, he presented a pulsating lesion in the right preauricular region and slight weakness in the territory of the inferior buccal branch of the facial nerve. The physical examination suggested an arterial lesion superficial to the facial nerve. However, in the operating theater, a section of the posterior and lateral flanks of the external carotid artery inside the parotid gland was identified. No lesion of the facial nerve was observed, and the external carotid artery was repaired. To better understand the anatomical rationale of this uncommon clinical case, we dissected the preauricular region of six cadavers previously injected with colored latex solutions in the vascular system. A small triangular space between the two main branches of division of the facial nerve in which the external carotid artery was not covered by the facial nerve was observed bilaterally in all cases.ConclusionsThis clinical case illustrates that, in a preauricular wound, the external carotid artery can be injured without facial nerve damage. However, no similar description was found in the reviewed literature, which suggests that this must be a very rare occurrence. According to the dissection study performed, this is due to the existence of a triangular space between the cervicofacial and temporofacial nerve trunks in which the external carotid artery is not covered by the facial nerve or its branches.

CT incidence of Morel-Lavallee lesions in patients with pelvic fractures: a 4-year experience at a level 1 trauma center.

The aim of this study is to determine the incidence and location of Morel-Lavallee lesions (MLLs) on pelvic CTs performed in evaluation of pelvic fractures and determine if correlation exists between MLLs and mechanism of injury or pelvic ring injury pattern. A retrospective review was performed of pelvic CTs on 1493 consecutive patients presenting with pelvic fractures at our level 1 trauma center. MLLs occurred in 182 of 1493 patients presenting with pelvic fractures. Statistical significance in MLL incidence was found across mechanism of injuries with MLLs being seen most frequently in MCC/ATV accidents and crush injuries. A little over half of MLLs occurred over the lateral thigh with almost all other MLLs occurring over the posterior (flank or lumbar) region. MLLs were much more common in vertical shear and spinopelvic dissociation pelvic ring fracture patterns compared to lateral compression and AP compression patterns. In lateral compression injuries, MLLs most commonly occurred over the thigh. In all other pelvic ring injury patterns, MLLs were predominately posterior. MLL's are not as rare as previously believed. The lateral thigh and lumbar/flank regions should be closely inspected on pelvic trauma patients to identify MLLs, particularly in patients with a spinopelvic dissociation injury pattern.

Invivo anticancer activity of maesopsin 4-O-β-glucoside isolated from leaves of Artocarpus tonkinensis A. Chev. Ex Gagnep.

To investigate the antitumor effect of maesopsin 4-O-β-glucoside (TAT2) isolated from the leaves of Artocarpus tonkinensis (A.tonkinensis) A. Chev. ex Gagnep. The antitumor activity of TAT2 was evaluated in Lewis lung carcinoma (LLC) tumor-bearing mice. BALB/c mice had tumors induced by implantation with 2×10(6) LLC cells into the subcutaneous right posterior flank. Tumor-bearing mice were treated orally with a range of doses of TAT2 and a standard drug, doxorubicin. Animals were observed for tumor growth and mortality rate. Blood was collected to determine hematological and biochemical parameters. TAT2 was isolated from an ethanolic extract of A.tonkinensis leaves. Its structure was determined by MS and NMR spectroscopy, and identified as TAT2. The compound did not show acute toxicity at the highest dose tested (2000mg/kg body weight). TAT2 exhibited antitumor activity by decreasing tumor growth, increasing the survival rate, and ameliorating some hematological and biochemical parameters at doses of 100 and 200mg/kg body weight (P<0.05). These results indicate that TAT2 possesses clear antitumor activity. Due to its bioavailability and low toxicity, and the fact that it could be isolated in a large scale from A.tonkinensis leaves, the compound shows promise as a potential anticancer drug.

Distribution of traumatic injuries after the installation of complete dentures in adult patients

AimDescribe the location of traumatic lesions of the oral mucosa that develop after the installation of complete dentures, as well as to quantify the number of post-operative controls that are required. A descriptive study was conducted by examining 84 patients who attended the dental center of Universidad de Los Andes, San Bernardo, during the period from July 2012 to July 2013. A sample of 120 edentulous patients was obtained. After the fabrication and installation of the complete dentures, at least 3 post-operative controls were performed and the location of oral lesions was recorded. Documentation of the association between the patient's clinical variables and the appearance of oral lesions during the first 3 controls was performed using a logistic regression. ResultsFor maxillary dentures, 5 post-operative visits were made and 6 controls for mandible dentures. In the upper jaw the anatomical areas of higher incidence of traumatic injuries were: canine fossa (23.9%), average bridle (23.1%), and distobuccal sulcus (20.1%). In the lower jaw, the highest number of lesions were recorded on the anterior lingual flank (16.5%), anterior and posterior lingual flank (13.4%), and distobuccal sulcus (12.8%). A significant association was observed between subjects who reported consumption of cholesterol-lowering medications and the development of traumatic lesions of the oral mucosa (OR: 0.25 and 95% CI: 0.055–0.939). The installation of complete dentures does not determine that the treatment has ended. Post-operative controls are needed to assess areas of erythema and ulceration.

Abstract B24: Natural withanolides: A new group of anticancer drugs that selectively target the PI3K-mTOR pathway as novel potent therapeutics against colon cancers in vitro and in vivo

Abstract Background: Current targeted inhibitors for colon cancer can reduce tumor burdens or stabilize disease, but are limited by their toxicity and lack of durable efficacy. Efforts continue to identify novel agents for this disease and newer multi-kinase inhibitors are currently being evaluated in clinical trials. Novel natural withanolides have been shown to selectively inhibit the PI3K-Akt-mTOR pathway in vitro and in vivo in adrenal cancer and medullary thyroid cancers. We hypothesize that this new class of drug compounds will be potent, selectively targeted inhibitors of this pathway network in colon cancers in vitro as well as in vivo as a promising novel therapeutics for this disease. Methods: In vitro: Withaferin A (WA), withalongolide A (WGA) and acetylated derivatives of each were first tested for anticancer effect on tumor cell viability on 5 different colon cancer lines (SW48, SW480, HT-29, SW-620, HCT-116) by MTS assay, then for apoptosis by flow cytometry and confirmed by western analysis for caspase 3 activation and PARP cleavage. PI3K-mTOR inhibition was confirmed by western blot analysis for total and phosphorylated levels of: mTOR, Akt, 4EBP1, p70-S6K; as well as for specific effects on colon cancer regulatory pathways including: GSK3β, β-catenin, Notch1 cleavage, and cyclin D1. In vivo: Athymic nude mice were injected with 10^7 HT-29 human colon cancer-cells in the left posterior flank and treated x 21days once tumors were &amp;gt;100mm3(N=10/drug) and followed for endpoints of toxicity (decreased body weight or body score),tumor growth&amp;gt;1500mm3 and survival. Results: IC50 levels of the parent compound WA averaged 640nM whereas the acetylated derivatives were as low as 30-100nM in the 5 cell lines compared to 4500nM in normal fibroblast cells. The withanolides potently induced apoptosis (starting at 250-500nM drug) on flow cytometry and this was confirmed by caspase 3 activation and PARP cleavage on Western analysis. These drugs also selectively inhibited phosphorylation of mTOR, Akt, 4EBP1, and p70S6K in a dose-dependent manner in the colon cancer lines starting at only 500nM of drug. Specific to colon cancers, the withanolides modulated GSK3β, β-catenin, Notch1 cleavage, and cyclin D1 levels in a dose-dependent manner all more potently than targeted tyrosine kinase inhibitors like ventadenib and cabozantenib which did not inhibit the PI3K-mTOR pathway. In vivo, all control animals progressed to metastatic disease to the liver and a terminal study endpoint within 6 weeks. All treatment arms inhibited HT-29 colon cancer growth at varying rates during the treatment period with only the WA treatment arm at 8mg/kg/day demonstrating a complete pathologic response to treatment in 80% of mice (p&amp;lt;0.001 vs controls with a tumor increase of 363±31% by day 21); (p&amp;lt;0.001 vs. vandetanib or cabozantenib 31-282% increase by day 21 respectively). WA-treated mice also had 100% survival after 8wks vs. all other arms(0-71%survival;p&amp;lt;0.01). Body weight loss during treatment was worst with vandetanib (18.5±1.3%) and cabozantinib (6.85±1.8%) compared to the withanolide treatment arms(p&amp;lt;0.01) with return to baseline weight by week 5. Conclusions: Natural withanolides are a novel class of chemotherapy drugs that selectively target PI3K-mTOR in colon cancers and demonstrate potent efficacy in vitro and in vivo compared to TKIs being evaluated in clinical trials with improved tolerability and less toxicity in vivo. These compounds warrant further evaluation to determine their clinical potential in this disease. Citation Format: Chitra Subramanian, Peter White, Alicia Gingrich, Barbara N. Timmermann, Mark Steven Cohen. Natural withanolides: A new group of anticancer drugs that selectively target the PI3K-mTOR pathway as novel potent therapeutics against colon cancers in vitro and in vivo. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr B24.

PD-1 Blockade Enhances Radiation Therapy-Induced Abscopal Effect

PD-1 Blockade Enhances Radiation Therapy-Induced Abscopal Effect

Thalidomide promotes leukocytosis in mice inoculated with 4T1 mammary carcinoma

The aim of this study was to evaluate the therapy effect of thalidomide in the 4T1 murine mammary carcinoma. 4T1 cell suspension was injected into the posterior left flank of all animals to obtain solid tumors. Five days after inoculation, the treatment group was orally administered 150 mg/kg of thalidomide for seven days. Tumors were measured every 48 hours until the end of treatment. Whole blood was collected for hematology analysis. Our results suggest that thalidomide therapy increase the number of circulating leukocytes in the 4T1 murine mammary carcinoma, and this response is accompanied by a decrease in tumor growth.

Aphanius arakensis, a new species of tooth-carp (Actinopterygii, Cyprinodontidae) from the endorheic Namak Lake basin in Iran.

A new species of tooth-carp, Aphanius arakensis sp. n., is described from the Namak Lake basin in Iran. The new species is distinguished by the congeners distributed in Iran by the following combination of characters: 10–12 anal fin rays, 28–32 lateral line scales, 10–13 caudal peduncle scales, 8–10 gill rakers, 12–19, commonly 15–16, clearly defined flank bars in males, a more prominent pigmentation along the flank added by relatively big blotches in the middle and posterior flank segments in females, a short but high antirostrum of the otolith that has a wide excisura, and a ventral rim with some small, drop-like processes, and 19 molecular apomorphies (17 transitions, two transversions) in the cytochrome b gene. It was suggested based on the phylogenetic analysis that the new species is sister to Aphanius sophiae from the Kor River and that Aphanius farsicus from the Maharlu Lake basin is sister to Aphanius arakensis plus Aphanius sophiae. A noticeable feature of the Aphanius diversity in Iran is the conservatism of the external morphology as well as morphometric and meristic characters, while distinctive differences are present in genetic characters, otolith morphology, and male color pattern. Transformation of the latter was probably driven by sexual selection.