Accessory left testicular artery in association with double renal vessels: a rare anomaly

A rare association of accessory testicular artery along with double renal arteries and accessory renal vein was observed unilaterally on the left side. In addition, the left inferior phrenic artery was arising from the left gastric branch of the coeliac trunk. This was observed in the dissection of an adult male cadaver during a routine undergraduate teaching programme. In this case, the accessory left testicular artery originated superior to the normal testicular artery from the descending abdominal aorta immediately below the origin of the normal left renal artery. In addition to this artery, a variant renal artery was noted with three segmental branches before entering the hilum. The accessory renal vein emerged from the lower pole after the receiving testicular vein joined the main renal vein. The left inferior phrenic artery arose from the left gastric branch of the coeliac trunk. An anatomical description of this uncommon variation is presented in this case report, highlighting its clinical implications. (Folia Morphol 2011; 70, 4: 309–311

Anatomical variations of testicular artery: a review

The testicular arteries (TAs) also known as internal spermatic arteries are long and slender arteries usually arising from the anterolateral aspect of the abdominal aorta, 2.5 cm to 5 cm caudal to the renal arteries. The variation in TAs may be found with respect to their origin, number or course. They can originate from the abdominal aorta itself at an abnormal level. If not arising from abdominal aorta the TA variants may arise from renal artery, suprarenal artery or any one of the lumbar arteries. Rarely it can arise from common or internal iliac artery, or from the superior epigastric artery. The most common variation with respect to origin of TA was found in association with renal vessels. In regard to their number, double TA was found to be most common and with respect to course most common variation was arched TA over ipsilateral renal vein. The arched TA at times on right side had a retrocaval course. Occurrence of TA variants is explained with embryology and the knowledge of its clinical significance is essential for future surgeons for designing vascular surgeries. Four studies had attempted to classify TA variants regarding their origin, number and course but they could not accommodate recently found TA variants. This led to our new proposed classification

Bilateral superficial ulnar artery with high origin from the axillary artery: its anatomy and clinical significance

The superficial ulnar artery (SUA) is a rare anatomical variant that usually arises either in the axilla or the arm and runs a superficial course in the forearm, enters the hand, and participates in the formation of superficial palmar arch. During the routine dissection of cadavers in the department of anatomy, whilst preparing the specimen for medical students, an unusual bilateral branch of the axillary artery was found in one of the cadavers: a rare variant of the artery known as SUA, which originates from the 2nd part of the axillary arteries of both sides. The SUA is a known anatomical variant, but the bilateral high origin from the 2nd part of the axillary artery is extremely unusual. Its occurrence is of great clinical importance to the surgical and radiological departments

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

3-Methylbenzo[1,2-c:5,4-c′]dichromen-6(8H)-one

The title compound, C21H14O3, crystallizes with eight independent molecules (A–H) in the asymmetric unit which are arranged in four groups of two molecules each (AB, CD, EF and GH). In each molecule, the pyran-2-one ring is planar (r.m.s. deviations vary from 0.001 to 0.017 Å), while the pyran ring has a screw-boat conformation. In the crystal, molecules stack in two columns, along the [10-1] direction, composed of molecules C, B, E and G, and D, A, F and H. Molecules A and F are linked via C—H...O hydrogen bonds. In addition, there are a number of C—H...π contacts present involving all of the molecules. These interactions result in the formation of a three-dimensional network

Evaluation of Antipyretic Activity of Siddha Herbomineral Formulation - Surangusa Parpam

The aim of the present study was to assess the antipyretic activity of Siddha herbo-mineral formulation Surangusa Parpam at the dose level of 15mg/kg and 35mg/kg body weight, orally, in brewer yeast induced fever model Wistar rats. Fever was induced by subcutaneous injection of 10ml/kg of 20% w/v aqueous suspension of brewer’s yeast into the nape of the rat's neck. After eighteen hours feverish animals were treated with Surangusa Parpam 15mg/kg and 35mg/kg body weight, orally, and rectal temperatures were evaluated at 0, 1, 2 and 3 hours post-treatment by inserting a well-lubricated bulb of the clinical thermometer. Surangusa Parpam showed a significant decrease in the elevated body temperature of rats that remained sustained throughout the tested time points from 1 to 3 hours in the used model. 35mg/kg body weight dose level showed significant inhibition of elevated body temperature when compared with the standard control. These results indicate that the Antipyretic activity of Surangusa Parpam and in addition to its well-established anti-inflammatory activity possesses significant antihistamine activity that may be beneficial in symptomatic relief when it is used in the therapy of allergic and inflammatory disorders