The role of circular RNAs (circRNAs) as a prognostic factor in lung cancer: a meta-analysis.

BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide. Among various histological types of lung cancer, majority are non-small cell lung cancer (NSCLC) which account for > 80%. Circular RNAs (circRNAs) are widely expressed in various cancers including lung cancer and implicated in tumourigenesis and cancer progression. This study aimed to systematically evaluate the prognostic values of circRNAs in lung cancer. METHODS: A systematic literature search was done in PubMed, Embase, and MEDLINE databases to select the eligible studies which reported the association between the expression of circRNAs and overall survival (OS) or disease-free survival (DFS) in histopathologically diagnosed lung cancer patients. The pooled hazard ratio (HR) and 95% confidence interval (CI) were assessed to determine the prognostic significance of circRNAs. RESULTS: A total of 43 studies were eligible for this meta-analysis (MA). 39 different types of circRNAs were reported: 28 showing upregulating and 11 showing downregulating action in lung cancer. High expression of circRNAs with upregulating action in lung cancer was associated with worse prognosis and poor OS (HR 1.93, 95% CI [1.61-2.33], p < 0.00001). High expression of circRNAs with downregulating action in lung cancer was associated with favorable OS and prognosis (HR 0.73, 95% CI [0.58-0.94], p = 0.01). However, there was no statistically significant association between high and low expression of both upregulating and downregulating circRNAs and DFS (HR 1.44, 95% CI [0.92-2.24], p = 0.11). CONCLUSIONS: This MA confirmed the pivotal role of circRNAs as important prognostic biomarkers for lung cancer, especially NSCLC. High expression of upregulating circRNAs is associated with poor prognosis; however, high expression of downregulating circRNAs is associated with favorable prognosis. Therefore, downregulatory action of circRNAs should be considered a promising treatment in the management of lung cancer, especially NSCLC.

Combined atezolizumab and nab-paclitaxel in the treatment of triple negative breast cancer: a meta-analysis on their efficacy and safety.

BACKGROUND: Triple negative breast cancer (TNBC) is clinically aggressive breast cancer with a poor prognosis. Approximately 20% of TNBC has been found to express programmed death ligand 1 (PD-L1), making it a potential therapeutic target. As a PD-L1 inhibitor, atezolizumab is a recently approved immunotherapeutic drug for TNBC, this meta-analysis (MA) was aimed to review the randomized controlled trial studies (RCTs) of combined atezolizumab and nab-paclitaxel in the treatment of TNBC and synthesize the evidence-based results on its effectiveness and safety. METHOD: We searched PubMed, Embase, EBSCOhost and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of combined atezolizumab and nab-paclitaxel with nab-paclitaxel alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs). RESULTS: A total of six RCTs were included in this MA. For efficacy, although OS was not significantly prolonged with combined atezolizumab and nab-paclitaxel (HR 0.90, 95% CI [0.79, 1.01], p=0.08), this combination therapy significantly improved PFS (HR 0.72, 95% CI [0.59, 0.87], p=0.0006) and ORR (RR 1.25, 95% CI [0.79, 1.01] p<0.00001). For safety, any AEs, haematological, gastrointestinal, and liver AEs showed no statistically significant differences between the atezolizumab and nab-paclitaxel combination group and nab-paclitaxel alone group. However, serious AEs, high grade, dermatological, pulmonary, endocrine, and neurological AEs were significantly lower with nab-paclitaxel alone compared to atezolizumab and nab-paclitaxel combined (p-value range from <0.00001 to 0,02). CONCLUSION: Atezolizumab combined with nab-paclitaxel was associated with improved outcomes in the treatment of TNBC; however, this combination resulted in more toxicity compared to nab-paclitaxel alone. While nab-paclitaxel alone produced chemotherapy-related AEs, the combination of atezolizumab with nab-paclitaxel produced AEs, especially immune-related AEs such as haematological, pulmonary, endocrine, and neurological AEs. TRIAL REGISTRATION: This research work of systematic review has been registered on PROSPERO (Registration number: CRD42022297952).

Role of coaggregation in the pathogenicity and prolonged colonisation of Vibrio cholerae.

Cholera is an acute diarrheal illness caused by the Gram-negative bacterium Vibrio cholerae. The pathogen is known for its ability to form biofilm that confers protection against harsh environmental condition and as part of the colonisation process during infection. Coaggregation is a process that facilitates the formation of biofilm. In a preliminary in vitro study, high coaggregation index and biofilm production were found between V. cholerae with human commensals namely Escherichia coli and Enterobacter cloacae. Building upon these results, the effects of coaggregation were further evaluated using adult BALB/c mouse model. The animal study showed no significant differences in mortality and fluid accumulation ratio between treatment groups infected with V. cholerae alone and those infected with coaggregation partnership (V. cholerae with E. coli or V. cholerae with E. cloacae). However, mild inflammation was detected in both partnering pairs. Higher density of V. cholerae was recovered from faecal samples of mice co-infected with E. coli and V. cholerae in comparison with other groups at 24 h post-infection. This partnership also elicited slightly higher levels of interleukin-5 (IL-5) and interleukin-10 (IL-10). Nonetheless, the involvement of autoinducer-2 (AI-2) as the signalling molecules in quorum sensing system is not evident in this study. Since E. coli is one of the common commensals, our result may suggest the involvement of commensals in cholera development.

Apoptotic activities in soft tissue sarcoma: immunohistochemical study and their association with tumour characteristics.

BACKGROUND: Many studies on the role of apoptosis in cancer development and management have been undertaken. Apoptotic activity depends partly on the balance between anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) activities. This study compared Bcl-2 and Bax expression in the tumour cells and endothelial cells of tumour blood vessels in soft tissue sarcoma, and examined the association of these with tumour characteristics. METHODS: A cross sectional (retrospective) study was conducted on 101 cases of various types of soft tissue sarcoma tumour cells and endothelial cells of tumour blood vessels. The immunohistochemical expressions of Bcl-2 and Bax were compared by correlating them according to site, size, depth, tumour margin, lymph node involvement, and histological type. RESULTS: Higher Bax than Bcl-2 expression in tumour cells was observed, although the difference was not statistically significant. There was a significant direct association between Bcl-2 and Bax in tumour cells with endothelial cells. Among tumour characteristics, the only significant correlation was that of the Bcl-2 expression in tumour cells with tumour histological subtypes (synovial sarcoma and leiomyosarcoma). CONCLUSION: The findings in this study support the role of endothelial cells in the survival and regression of tumour cells in tumour genesis. Therefore, inhibition of endothelial cell survival and activation, or induction of tumour cell apoptosis offers a promising prospect for tumour management.

Efficacy and Safety of Immune Checkpoint Inhibitors for Advanced Malignant Melanoma: A Meta-Analysis on Monotherapy Vs Combination Therapy.

Background: Immune checkpoint inhibitors (ICIs) are approved as cancer immunotherapeutic agents for advanced malignant melanoma (MM) in recent years, and nivolumab and ipilimumab are the most widely used ICIs either alone or in combination. However, their efficacy and safety between single and combined ICIs are not clear. This meta-analysis (MA) is aimed to update the efficacy and safety of ICIs by comparing monotherapy and combination therapy in the treatment of advanced MM. Method: We searched PubMed, Embase, EbscoHost and ClinicalTrials.gov for the eligible randomized controlled trials (RCTs) which compared the efficacy and safety of ICIs between a single ICI and combined ICIs. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on the study heterogeneity. Results: A total of nine RCTs were included in this MA. Regarding the efficacy, combined nivolumab and ipilimumab therapy showed statistically significant prolonged OS and PFS with HR 0.65, 95% CI [0.53, 0.79], p <0.0001 and HR 0.48, 95% CI [0.38, 0.60], p<0.0001 respectively. Combination therapy with nivolumab and ipilimumab also showed statistically significant longer ORR than monotherapy; with RR 2.15, 95% CI [1.63, 2.84], p <0.00001. In terms of safety, the incidence of all AEs which include any AEs, high-grade, haematological, gastrointestinal, dermatological, pulmonary, liver and endocrine AEs were significantly lower with monotherapy (either nivolumab or ipilimumab) of ICI compared to combination ICI therapy with a p-value <0.00001 to 0.03. Conclusion: Efficacy of the combined nivolumab and ipilimumab was better than a single ICI, especially in the treatment of advanced MM. Although combination therapy showed better efficacy than monotherapy, monotherapy (either nivolumab or ipilimumab) was safer than combination therapy as it tended to decrease the incidence of most of the treatment-related AEs.

Primary retroperitoneal serous adenocarcinoma: A case report of rare malignancy with literature review.

The primary retroperitoneal serous adenocarcinoma (PRSAC) is a rare malignant tumor of the retroperitoneum. It shares the same pathological and biological behavior with ovarian serous carcinoma. Most of the cases develop as peritoneal adenocarcinoma and rarely occur in the retroperitoneum. It is reported as serous surface papillary carcinoma of the peritoneum and extraovarian peritoneal serous papillary carcinoma. We present a case of PRSAC in a 60-year-old woman. Only 11 cases of PRSAC have been reported from 1983 to 2019. Histopathological features with immunohistochemical expressions are important to diagnose PRSAC. The outcome and survival mainly depend on the possibility of surgical resection. Molecular genetics of PRSAC should also be studied in relation with its ovarian counterpart.

Aspirin and Reducing Risk of Gastric Cancer: Systematic Review and Meta-Analysis of the Observational Studies.

BACKGROUND AND AIMS: The latest meta-analysis on the role of aspirin on various cancers was published in early 2018. By including the latest and updated primary observational studies, we aimed to conduct this systematic review and meta-analysis to synthesize stronger evidence on the role of aspirin in reducing gastric cancer (GC) risk. METHODS: The PubMed, Scopus, and MEDLINE databases were systematically searched up to December 2019 to identify relevant studies. Random-effects model was used to calculate summary ORs and 95%CI for I 2 >50%. If the heterogeneity is not significant, the fixed-effects model was used. Overall analysis of the studies, inverse variance weighting after transforming the estimates of each study into log OR and its standard error were used. RESULTS: 21 studies were included in this meta-analysis. Results showed that aspirin significantly reduced the GC risk (OR=0.64, 95%CI=0.54-0.76) with substantial heterogeneity (I 2 =96%). Effect of GC risk reduction in low dose (OR=0.80, 95%CI=0.59-1.09) is slightly greater than high dose aspirin (OR=1.08, 95%CI=0.77-1.52). Protective effect of aspirin uses >5 years (OR=0.67, 95%CI=0.34-1.31) was greater than <5 years (OR=1.01, 95%CI=0.72-1.43) Conclusion: In conclusion, this meta-analysis showed that low dose aspirin with longer duration of more than 5 years were associated with a statistically significant reduction in GC risk. However, due to possible confounding variables and bias, these results should be cautiously treated.

Expression of Vascular Endothelial Growth Factor and Its Receptors in Thyroid Nodular Hyperplasia and Papillary Thyroid Carcinoma: A Tertiary Health Care Centre Based Study

Introduction: Vascular endothelial growth factor (VEGF) is an angiogenic factor that plays an important role in thyroid cancer. VEGF is known to have high affinity to VEGF receptors such as VEGFR-1 (Flt-1) and VEGFR-2 (KDR). Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and studies showed the increasing incidence of PTC arising in nodular hyperplasia. Targeted therapy on these growth factors and receptors are used in management of both differentiated and undifferentiated thyroid carcinoma. This study aims to determine the expression of VEGF and VEGF receptors (VEGFR) in thyroid nodular hyperplasia and PTC. Methods: A cross-sectional study based on paraffinized archival tissue blocks of 113 nodular hyperplasias and 67 PTC from the thyroidectomy specimens in the year of 2003 to 2014. The tissue sections were then stained by immunohistochemistry for VEGF, VEGFR-1 and VEGFR-2. The lymph node involvement and extrathyroid extension also were determined. Results: The mean age of PTC patients was 44.7±15.8 years and nodular hyperplasia were 42.2±13.6 years. There was a statistical difference of VEGFR-1 (p=0.028) and VEGFR-2 (p=0.003) expression between nodular hyperplasia and PTC. However, no significant difference of VEGF expression (p=0.576) between both diseases. Co-expression of VEGF and VEGFR-1 was significant in both nodular hyperplasia (p=0.016) and PTC (p=0.03), meanwhile no relevant relationship for VEGF and VEGFR-2 expression (p>0.05). No significant association (p>0.05) between lymph node status and extrathyroid extension with age groups, gender, VEGF and VEGFR expression. Conclusions: VEGF, VEGFR-1 and VEGFR-2 showed overexpression in both nodular hyperplasia and PTC. The expression of VEGFR-1 and VEGFR-2 are more significant in PTC with relevant co-expression of VEGF and VEGFR-1. Therefore, the inhibition of VEGFR offers a promising prospect for tumour management in thyroid carcinoma.

Evaluation of Chondroprotective Activity of Channa striatus in Rabbit Osteoarthritis Model.

OBJECTIVES: The objective of the study is to evaluate the chondroprotective activity of Channa striatus (Channa) and glucosamine sulphate (glucosamine) on histomorphometric examinations, serum biomarker, and inflammatory mediators in experimental osteoarthritis (OA) rabbit model. DESIGN: Anterior cruciate ligament transection (ACLT) was performed to induce OA in thirty-three male New Zealand white rabbits and were randomly divided into three groups: Channa, glucosamine, and control group. The control group received drinking water and the Channa and glucosamine groups were orally administered with 51.4 mg/kg of Channa extract and 77.5 mg/kg of glucosamine sulphate in drinking water, respectively, for eight weeks and then sacrificed. The articular cartilage was evaluated macroscopically and histologically using semiquantitative and quantitative methods. Serum cartilage oligomeric matric protein (COMP), cyclooxygenase 2 (COX-2) enzyme, and prostaglandin E2 (PGE2) were also determined. RESULTS: Macroscopic analysis revealed that Channa group have a significantly lower severity grade of total macroscopic score compared to the control (p < 0.001) and glucosamine (p < 0.05) groups. Semiquantitative histology scoring showed that both Channa and glucosamine groups had lower severity grading of total histology score compared to the control group (p < 0.001). In comparison with the control, Channa group had lower histopathological changes in three compartments of the joint compared to glucosamine group which had lower histological scoring in two compartments only. The cartilage thickness, area, and roughness of both Channa (p < 0.05) and glucosamine (p < 0.05) groups were superior compared to the control group. However, the Channa group demonstrated significantly less cartilage roughness compared to the glucosamine group (p < 0.05). Serum COMP levels were lower in both Channa (p < 0.05) and glucosamine (p < 0.05) groups compared to the control group. CONCLUSION: Both oral administration of Channa extract and glucosamine exhibited chondroprotective action on an ACLT OA-induced rabbit model. However, Channa was superior to glucosamine in maintaining the structure of the cartilage.

Poorly differentiated thyroid carcinoma: A hospital-based clinicopathological study and review of literature.

INTRODUCTION: Poorly differentiated thyroid carcinoma (PDTC) is a rare aggressive malignancy of thyroid follicular cells and has unique features in morphology and behavior. This study was aimed to describe the experience of a tertiary medical center with PDTC within a 10-year period. MATERIALS AND METHODS: This is a descriptive retrospective study of eight cases of PDTC among 418 various thyroid carcinomas. All cases of PDTC were retrieved along with the clinicopathological information. RESULTS: Only eight cases (1.9%) of PDTC were diagnosed among 418 thyroid carcinomas. Mean age was 48.12 with 3:5 (male:female) and tumor size ranged 3-12 cm. PDTC were diagnosed coexisting with one or more other pathologies; nodular hyperplasia (four cases), papillary carcinoma (one case), follicular carcinoma (three cases), and Hashimoto thyroiditis (two cases); with ≥60% PDTC component. Six cases associated with high-grade features died within 3 years after diagnosis. DISCUSSION: Mean age in this study was younger including a 20-year-old girl. Younger age was associated with better prognosis. Most of the cases had underlying benign thyroid lesions and differentiated thyroid carcinoma. Most of the PDTC had poor prognosis associated with PDTC component ≥60%, tumor necrosis, high mitotic count, lymph node involvement, vascular invasion and distant metastasis; and these cases died within 3 years after diagnosis. CONCLUSION: Although treatment of PDTC remains surgery followed by radioiodine therapy, correct histopathological diagnosis is important for clinicians and oncologists to predict the prognosis. All thyroid carcinoma should be sampled thoroughly not to miss small foci of PDTC component.

Bilateral Ovarian Clear Cell Carcinoma Arising in 17 Year Longstanding History of Bilateral Ovarian Endometriosis.

Clear cell carcinoma of ovary is uncommon ovarian tumour that arises from surface epithelium of ovary. It has well-known association with ovarian endometriosis. We report here the first case of bilateral clear cell carcinoma of ovaries in a 40-year-old woman with a 17-year history of bilateral ovarian endometriosis. In addition, during the longstanding duration of the endometriosis, the patient was treated with hormonal therapy, including oestrogen. It represents the first report of such bilateral involvement in the background of ovarian endometriosis. This should prompt clinicians to be aware that prolonged hormonal treatment of endometriosis may precipitate bilateral malignancy of the ovary.

Epidermal Regeneration of Cultured Autograft, Allograft, and Xenograft Keratinocytes Transplanted on Full-Thickness Wounds in Rabbits.

OBJECTIVES: Skin grafting has been evolving as an important application in reconstructive surgery. Mixed reports about the survival of allogeneic and xenogeneic keratinocytes require further substantiation to determine the role of these cells in wound healing. MATERIALS AND METHODS: Rabbit and rat skins were recovered and cultured in vitro. Full-thickness wounds were created on the dorsum of rabbits (2 cm × 2 cm; n = 4). Cultured epithelial autograft, allograft, and xenograft cells were sprayed onto 3 freshly created wounds, with 1 wound acting as a control. The wounds were monitored every 2 days for 4 weeks. After 4 weeks, the rabbits were killed; skin biopsies were taken from each healed wound and stained with hematoxylin and eosin, and epidermal thickness was measured. RESULTS: All examined grafts showed favorable healing outcomes because the wounds appeared similar to normal skin upon healing. The only observed significant difference was the thickness of the epidermis layer, which was thinner in the xenograft (P = .002) than the autograft or allograft. Morphologic evaluation of the skin surface showed that the rat skin was thinner than the rabbit skin. The graft that achieved the best result was the autograft because the thickness was similar to and mimicked normal skin. CONCLUSIONS: All 3 grafts (autograft, allograft, and xenograft) have the potential to reconstitute epithelial defects. This approach can overcome the limitation of autologous skin donor sites, especially in burn cases.

Relationship of angiogenic and apoptotic activities in soft-tissue sarcoma.

INTRODUCTION: Angiogenesis and apoptosis play an essential role in tumor development and progression. Previous studies on apoptosis and angiogenesis of soft-tissue sarcoma (STS) were done separately. This is the first study of the relationship between apoptotic and angiogenic activity. Correlation of expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax) in the tumor cells (TCs) with their expression in endothelial cell (EC) of the tumor blood vessels in STS were also carried out. MATERIALS AND METHODS: 101 cases of STS; consisting liposarcoma, malignant fibrous histiocytoma, synovial sarcoma, fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma and malignant peripheral nerve sheath tumor; were collected and immunohistochemical reaction of vascular endothelial growth factor (VEGF), Bcl-2 and Bax were examined. RESULTS: Higher Bax expression in TCs (54.5%) was seen compared to Bcl-2 expression (44.6%). There was a significant association between Bcl-2 and Bax in TCs with ECs. Significant association was also seen between histological types of STS with Bcl-2 expression; however not with Bax expression. There was an association between VEGF and Bax with high VEGF expression and weak Bax expression. However, VEGF expression was not associated with Bcl-2 expression and histological types. CONCLUSION: This study supports the role of ECs of tumor blood vessels and apoptosis of TCs in tumor management. Increased angiogenesis may inhibit apoptosis of TCs and lead to tumor growth. Therefore, inhibition of ECs survival or activation of ECs death is promising prospect for tumor therapy. Immunohistochemical antibodies in this study might be potential useful marker for the prognosis of STS.

Congenital mature cystic teratoma of the lateral neck presenting as cystic hygroma: a rare case report with literature review.

Teratoma of the neck is a rare extra-gonadal teratoma. Although it can be seen in adult, most of the cases present in fetal life or early childhood. Grading and classification of teratoma is important for management and prognosis. Decision making between mature and immature teratoma is sometime challenging if it is not composed of extensive unusual neuroectodermal tissue component. We reported a rare case of huge congenital mature cystic teratoma composted of various neuroectodermal tissues in an 8-month-old boy; it was located at the lateral neck and mimicked congenital cystic hygroma. A literature review was done to grade and classify the tumour.

Solid variant of papillary thyroid carcinoma in a 14-year-old girl.

Solid variant of papillary thyroid carcinoma (PTC) is a rare, poorly characterised variant and predominantly reported in children with a history of radiation exposure. This variant has a high propensity for extra-thyroidal extension and cervical lymph node metastases. A 14-year-old Malay girl who had no history of radiation exposure, presented with multiple cervical lymphadenopathy and it was clinically suspicious for tuberculosis or lymphoma. An incisional biopsy revealed a metastatic PTC. The patient underwent total thyroidectomy with bilateral lateral neck dissection and histopathology report was solid variant of PTC. Whole-body I(131) scan was performed which revealed an intense tracer uptake in the neck. She was planned for radioactive iodine ablation and now on regular follow-up for monitoring of possible tumour metastasis.