Durvalumab and taxane family combination therapy enhances the antitumoral effects for NSCLC: An in vitro study

Immunotherapy has lately become the most preferred cancer treatment method, and for non-small cell lung cancer (NSCLC) first-line treatment, there are many immunotherapy options. This study aimed to assess the effectiveness and toxicity of paclitaxel (PTX), docetaxel (DTX) chemotherapy, immune checkpoint inhibitor treatment (durvalumab; DVL), and their combination in NSCLC. A-549 cells were treated with DVL in combination with PTX and DTX (a quarter of the IC₅₀) to investigate their anticancer effects on these cells. The MTT assay, wound healing tests, and double-staining with Annexin V/PI were used to assess the cell viability, apoptosis, and migration. The results showed that a combination of 0.35 mg/mL DVL with 6.5 μg/mL PTX and 1.75 μg/mL DTX produced a synergistic effect with CI values of 0.88, 0.37, and 0.81, respectively. Moreover, the PTX + DTX + DVL combination led to a significantly increased apoptotic rate up to 88.70 ± 3.39% in the A549 cell line compared to monotherapy (p < .001). In addition, we found that the combination therapy with these agents increased the expression level of Bax, Cas-3, p53, and Bax/Bcl-2 ratio in all experimental groups. In conclusion, the results suggest that combining anti-PD-L1 antibody therapy with chemotherapy may provide a promising approach to enhance treatment outcomes and be a potentially efficacious strategy for treating NSCLC patients. Further research and clinical investigations are needed to elucidate the underlying molecular mechanisms and validate the therapeutic potential of these compounds in vivo.     

Intraosseous angiosarcoma with secondary aneurysmal bone cysts presenting as an elusive diagnostic challenge

Angiosarcoma of bone is an exceedingly rare primary bone malignancy that can present as an aggressive osteolytic lesion. Histological diagnosis can be extremely challenging, as the pathological features often resemble that of aneurysmal bone cysts. We report an interesting and peculiar case of an intraosseous angiosarcoma that presented as a diagnostic dilemma and discuss the relevant radiological and pathologic findings.     

Comparison between partial ulnar and intercostal nerve transfers for reconstructing elbow flexion in patients with upper brachial plexus injuries

The present study was designed to investigate the ameliorative potential of Ocimum sanctum and its saponin rich fraction in vincristine-induced peripheral neuropathic pain in rats. Peripheral neuropathy was induced in rats by administration of vincristine sulfate (50 μg/kg i.p.) for 10 consecutive days. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species (TBARS), super-oxide anion content (markers of oxidative stress) and total calcium levels were measured. Vincristine administration was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia. Furthermore, vincristine administration was also associated with an increase in oxidative stress and calcium levels. However, administration of Ocimum sanctum (100 and 200 mg/kg p.o.) and its saponin rich fraction (100 and 200 mg/kg p.o.) for 14 days significantly attenuated vincristine-induced neuropathic pain along with decrease in oxidative stress and calcium levels. It may be concluded that Ocimum sanctum has ameliorative potential in attenuating chemotherapy induced-painful neuropathic state, which may be attributed to decrease in oxidative stress and calcium levels. Furthermore, saponin rich fraction of Ocimum sanctum may be responsible for its noted beneficial effect in neuropathic pain in rats.     

Regulation of tumor angiogenesis by microRNAs: State of the art

MicroRNAs (miRNAs, miRs) are small (21–25 nucleotides) endogenous and noncoding RNAs involved in many cellular processes such as apoptosis, development, proliferation, and differentiation via binding to the 3′-untranslated region of the target mRNA and inhibiting its translation. Angiogenesis is a hallmark of cancer, which provides oxygen and nutrition for tumor growth while removing deposits and wastes from the tumor microenvironment. There are many angiogenesis stimulators, among which vascular endothelial growth factor (VEGF) is the most well known. VEGF has three tyrosine kinase receptors, which, following VEGF binding, initiate proliferation, invasion, migration, and angiogenesis of endothelial cells in the tumor environment. One of the tumor microenvironment conditions that induce angiogenesis through increasing VEGF and its receptors expression is hypoxia. Several miRNAs have been identified that affect different targets in the tumor angiogenesis pathway. Most of these miRNAs affect VEGF and its tyrosine kinase receptors expression downstream of the hypoxia-inducible Factor 1 (HIF-1). This review focuses on tumor angiogenesis regulation by miRNAs and the mechanism underlying this regulation.     

Myoepithelioma within the carpal tunnel: a case report and review of the literature

Myoepitheliomas of the extremity are rare and usually benign, while a minority display malignant features. This case demonstrates the diagnosis and management of myoepithelioma within the carpal tunnel. Clinical and radiological tumour features were evaluated. Hematoxylin and eosin stained tumour sections were examined, and immunohistochemistry was performed. Histology revealed a nodular mass of epithelioid cells in clusters within a myxoid/chondroid stroma. No mitoses were noted. Cytokeratins, neuron-specific enolase, synaptophysin, glial fibrillary acidic protein, and S100 were positive on immunohistochemistry. A literature review revealed very few prior reports of myoepithelioma in the wrist, and limited data concerning any relationship between recurrence and quality of surgical margins. In this case, wide local excision would have significantly compromised dominant hand function, and therefore a marginal excision was deemed appropriate in the context of bland histological features. Surgical margins noted in future case reports will aid clinical decision making.     

Dynamics of spatial heterogeneity of stomatal closure in Tradescantia virginiana altered by growth at high relative air humidity

The spatial heterogeneity of stomatal closure in response to rapid desiccation of excised well-watered Tradescantia virginiana leaves grown at moderate (55%) or high (90%) relative air humidity (RH) was studied using a chlorophyll fluorescence imaging system under non-photorespiratory conditions. Following rapid desiccation, excised leaves grown at high RH had both a greater heterogeneity and a higher average value of PSII efficiency (Phi(PSII)) compared with leaves grown at moderate RH. Larger decreases in relative water content resulted in smaller decreases in water potential and Phi(PSII) of high RH-grown leaves compared with moderate RH-grown leaves. Moreover, the Phi(PSII) of excised high RH-grown leaves decreased less with decreasing water potential, implying that the stomata of high RH-grown leaves are less sensitive to decreases in leaf water potential compared with moderate RH-grown leaves. After desiccation, some non-closing stomata were distributed around the main vein in high RH-grown leaves. Direct measurements of stomatal aperture showed 77% stomatal closure in the margins after 2 h desiccation compared with 40% closure of stomata in the main-vein areas in high RH-grown leaves. Faster closure of stomata in leaf margins compared with main-vein areas of leaves grown at high RH was related to substantially lower relative water content in these areas of the leaves.     

Seed Priming with Cold Plasma and Multi-walled Carbon Nanotubes Modified Growth,Tissue Differentiation,Anatomy, and Yield in Bitter Melon (Momordica charantia)

Journal of Plant Growth Regulation - This study was conducted to explore the capability of seed priming with the cold plasma and multi-walled carbon nanotubes (MWCNT), in order to improve growth...     

Evaluation of the novel folate receptor ligand [18F]fluoro-PEG-folate for macrophage targeting in a rat model of arthritis

Introduction

Detection of (subclinical) synovitis is relevant for both early diagnosis and monitoring of therapy of rheumatoid arthritis (RA). Previously, the potential of imaging (sub)clinical arthritis was demonstrated by targeting the translocator protein in activated macrophages using (R)-[¹¹C]PK11195 and positron emission tomography (PET). Images, however, also showed significant peri-articular background activity. The folate receptor (FR)-β is a potential alternative target for imaging activated macrophages. Therefore, the PET tracer [¹⁸F]fluoro-PEG-folate was synthesized and evaluated in both in vitro and ex vivo studies using a methylated BSA induced arthritis model.

Methods

[¹⁸F]fluoro-PEG-folate was synthesized in a two-step procedure. Relative binding affinities of non-radioactive fluoro-PEG-folate, folic acid and naturally circulating 5-methyltetrahydrofolate (5-Me-THF) to FR were determined using KB cells with high expression of FR. Both in vivo [¹⁸F]fluoro-PEG-folate PET and ex vivo tissue distribution studies were performed in arthritic and normal rats and results were compared with those of the established macrophage tracer (R)-[¹¹C]PK11195.

Results

[¹⁸F]fluoro-PEG-folate was synthesized with a purity >97%, a yield of 300 to 1,700 MBq and a specific activity between 40 and 70 GBq/µmol. Relative in vitro binding affinity for FR of F-PEG-folate was 1.8-fold lower than that of folic acid, but 3-fold higher than that of 5-Me-THF. In the rat model, [¹⁸F]fluoro-PEG-folate uptake in arthritic knees was increased compared with both contralateral knees and knees of normal rats. Uptake in arthritic knees could be blocked by an excess of glucosamine-folate, consistent with [¹⁸F]fluoro-PEG-folate being specifically bound to FR. Arthritic knee-to-bone and arthritic knee-to-blood ratios of [¹⁸F]fluoro-PEG-folate were increased compared with those of (R)-[¹¹C]PK11195. Reduction of 5-Me-THF levels in rat plasma to those mimicking human levels increased absolute [¹⁸F]fluoro-PEG-folate uptake in arthritic joints, but without improving target-to-background ratios.

Conclusions

The novel PET tracer [¹⁸F]fluoro-PEG-folate, designed to target FR on activated macrophages provided improved contrast in a rat model of arthritis compared with the accepted macrophage tracer (R)-[¹¹C]PK11195. These results warrant further exploration of [¹⁸F]fluoro-PEG-folate as a putative PET tracer for imaging (sub)clinical arthritis in RA patients.     

Length‐weight relationships of Turcinoemacheilus kosswigi Bănărescu and Nalbant, 1964 (Teleostei:Nemacheilidae) in southwestern Iran and its relation to habitat structure

Length‐weight relationships of Turcinoemacheilus kosswigi, based on 56 individuals from two newly discovered localities in the Iranian Tigris drainage, are reported for the first time. These new localities have the same structural characters as already‐reported habitats, but the species was found in much higher altitudes than before.