miR-1293 acts as a tumor promotor in lung adenocarcinoma via targeting phosphoglucomutase 5

Background Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Studies have found that miR-1293 is related to the survival of LUAD patients. Unfortunately, its role in LUAD remains not fully clarified. Methods miR-1293 expression and its association with LUAD patients’ clinical characteristics were analyzed in TCGA database. Also, miR-1293 expression was detected in LUAD cell lines. Cell viability, migration, invasion and expression of MMP2 and MMP9 were measured in LUAD cells following transfection with miR-1293 mimic or antagomir. Phosphoglucomutase (PGM) 5 was identified to be negatively related to miR-1293 in LUAD patients in TCGA database, and their association was predicated by Targetscan software. Hence, we further verified the relationship between miR-1293 and PGM5. Additionally, the effect and mechanism of miR-1293 were validated in a xenograft mouse model. Results We found miR-1293 expression was elevated, but PGM5 was decreased, in LUAD patients and cell lines. Higher miR-1293 expression was positively related to LUAD patients’ pathologic stage and poor overall survival. miR-1293 mimic significantly promoted, whereas miR-1293 antagomir suppressed the viability, migration, invasion, and expression of MMP2 and MMP9 in LUAD cells. PGM5 was a target of miR-1293. Overexpression of PGM5 abrogated the effects of miR-1293 on the malignant phenotypes of LUAD cells. Administration of miR-1293 antagomir reduced tumor volume and staining of Ki-67 and MMP9, but elevated PGM5 expression in vivo. Conclusions miR-1293 promoted the proliferation, migration and invasion of LUAD cells via targeting PGM5, which indicated that miR-1293 might serve as a potential therapeutic target for LUAD patients.

Subungual Melanoma: A Single Institution Experience

Despite the changing paradigms of melanoma treatment in recent years, there remains a relative paucity of data regarding subungual melanoma in the literature. From 2002–2018, 25 patients with subungual melanoma were surgically treated at our facility. A retrospective chart review was conducted to collect relevant demographic, clinical, pathologic, and outcomes data. The median age at diagnosis was 69 years. Most patients (60%) were male, and the melanoma lesion was most often located on the foot (68%). Acral-lentiginous was the most common histologic subtype (59%), and the median Breslow thickness was 3.4 mm. Fifteen patients (63%) underwent a sentinel lymph node biopsy as part of their surgical resection, and four of these patients (27%) had metastatic disease in the lymph nodes. In total, 10 patients underwent lymph node dissection of the involved basin. The median follow up was 21 months in this patient population. Age, gender, tumor location, ulceration, and lesion histology were not significantly associated with recurrence free survival (RFS). Increasing Breslow thickness was found to be significantly associated with shorter RFS (HR: 1.07, CI: 1.03–1.55). In total, 13 patients developed a disease recurrence, and RFS rates were 66% at 1 year and 40% at 3 years. Additionally, 91 and 37% of patients were alive at one year and three years, respectively. Subungual melanomas are rare lesions that often have a more advanced stage at diagnosis, which contributes to the poor prognosis of these cutaneous malignancies.

Lipid metabolic transcriptome-wide profile and signature of lung adenocarcinoma

Background: Lung cancer is the cancer with high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. The disorder of lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on diagnosis and prognostic biomarkers of LUAD. Methods: In this study, we performed an expression analysis of 1045 lipid metabolism-related genes between LUAD tumors and normal tissues from the TCGA-LUAD cohort. The interaction network of differential expression genes (DEGs) was constructed to identify. The association between hub genes and overall survival (OS) was evaluated and formed a model to predict the prognosis of LUAD using a nomogram, and the model was validated by another cohort (GSE13213). Results: Finally, a total of 217 lipid metabolism-related DEGs were detected in LUAD. They were significantly enriched in glycerophospholipid and steroid metabolism . Then we identified 6 hub genes through network and cytoHubba, including INS , LPL , HPGDS , DGAT1 , UGT1A6 , and CYP2C9 . The high expression of CYP2C9 , UGT1A6 , and INS , whereas low expressions of DGAT1 , HPGDS , and LPL , were associated with worse OS for 719 LUAD patients. Our model found that the high-risk score group had a worse OS, and the validated cohort had the same result. Conclusion: This study constructed a signature of six lipid metabolic genes, which was significantly associated with the diagnosis and prognosis of LUAD patients. The gene signature can be used as a biomarker for LUAD in the term of lipid metabolic.

Activity of lenvatinib plus everolimus combination in a heavily pretreated patient with papillary renal cell carcinoma: a case report

Background: Papillary renal cell carcinoma (pRCC) represents the second most common histologic subtype of renal cell carcinoma and comprises 2 subtypes. Prognosis for type 2 is associated with poor clinical outcome. Current guidelines are based on phase II trials, phase III trials in patients with clear cell histology, or retrospective data. Case description: To our knowledge, we describe for the first time a case of a patient with heavily pretreated metastatic pRCC who benefited from the combination of lenvatinib plus everolimus for more than 2 years. Conclusion: According to immunohistologic and biological findings in our patient both on primary tumor and liver metastasis, we hypothesize that selected patients with metastatic pRCC, progressed to standard/available treatments (including angiogenic drugs, mTOR inhibitors, and immunotherapy) and dissociated response to everolimus, could benefit from adding lenvatinib to everolimus.

Analysis of Predictive Biomarkers in Patients With Lung Adenocarcinoma From Southern Brazil Reveals a Distinct Profile From Other Regions of the Country

PURPOSE Adenocarcinoma is the most common histologic subtype of non–small-cell lung cancer, representing 40% of all diagnoses. Several biomarkers are currently used to determine patient eligibility for targeted treatments, including analysis of molecular alterations in EGFR and ALK, as well as programmed death-ligand 1 (PD-L1) protein expression. Epidemiologic data reporting the frequency of these biomarkers in Brazilian patients with lung adenocarcinoma (LUAD) are limited, and existing studies predominantly included patients from the southeast region of the country. MATERIALS AND METHODS The goal of this study was to investigate the frequency of somatic mutations in the EGFR, KRAS, NRAS, and BRAF genes, ALK, and PD-L1 expression in a series of Brazilian patients diagnosed with LUAD predominantly recruited from centers in southern Brazil. Molecular analysis of the EGFR, KRAS, NRAS, and BRAF genes was performed by next-generation sequencing using DNA extracted from tumor tissue. Immunohistochemistry was used to detect ALK and PD-L1 expression. RESULTS Analysis of 619 tumors identified KRAS mutations in 189 (30.2%), EGFR mutations in 120 (19.16%), and BRAF mutations in 19 (3%). Immunohistochemistry demonstrated ALK and PD-L1 expression in 4% and 35.1% of patients, respectively. CONCLUSION To our knowledge, this is the first study investigating the molecular epidemiology of patients with LUAD from southern Brazil and the largest assessing the frequency of multiple predictive biomarkers for this tumor in the country. The study also reveals a distinct mutation profile compared with data originating from other regions of Brazil.

Bladder Stones Associated with an Aggressive Plasmacytoid Variant of Urothelial Cancer: A Rare Case and Literature Review

Urothelial carcinoma is the most common histologic subtype of bladder cancer, accounting for approximately 90%. We herein report a case of a 78-year-old man with an unusual association of bladder stones with an aggressive plasmacytoid variant of urothelial cancer. Initially he presented in 2009 with a very large bladder stone and was treated by an open cystolithotomy. Histology from a bladder biopsy at that time was benign. He failed to attend follow-up appointments but subsequently he attended in 2016 with a recurrent urinary tract infection and an acute kidney injury. A CT scan showed multiple bladder stones. The cause of our patients' multiple bladder stones is unclear and unusual. He then underwent a further open cystolithotomy according to our multidisciplinary team recommendation. Post-operatively he unfortunately developed a non-healing vesicocutaneous fistula for which he was performed cystoscopy and biopsy but ended with transurethral resection due to the extent of abnormal/necrotic tissue. Histology confirmed a plasmacytoid variant of urothelial cancer. To our knowledge, this is the first case of an association of bladder stones with a plasmacytoid variant of urothelial cancer.

First-Line Therapies for Metastatic Lung Adenocarcinoma Without a Driver Mutation

Lung cancer is the leading cause of cancer-related death worldwide. The majority of these cancers are non–small-cell lung cancer, of which adenocarcinoma is the most common histologic subtype. Most patients are diagnosed at advanced stages when systemic treatment is needed. Whereas prognosis has improved for patients with targetable driver mutations, the majority of patients do not possess tumors with such molecular mutations. Platinum-based chemotherapy has traditionally been the mainstay of treatment, although in recent years immunotherapy has emerged as a treatment option and can result in robust and durable treatment responses in a subset of patients. Recent clinical trials on novel immunotherapy combinations and immunochemotherapy combinations may broaden the number of patients that may benefit from checkpoint inhibitors and elicit responses in those who otherwise may not have experienced a response to monotherapy with an immunotherapy drug. This review will outline the currently available therapies for the first-line treatment of metastatic adenocarcinoma that do not possess a driver mutation and provide a recommended approach and algorithm by which to select the best first-line therapy.

Urachal adenocarcinoma - case report and literature review

Introduction. Urachal adenocarcinoma is extremely rare and comprises from 0.35% to 0.7% of all bladder tumors. The most common histologic subtype of urachal tumors is adenocarcinoma which can be associated with intestinal metaplasia and mucin production. Case report. We report a case of a 53-year-old patient who attented a urologist because of an intermittent haematuria lasting for three months. The ultrasound examination detected infiltration of the bladder at the fundus, 24 ? 29 mm in diameter. By the same wall, next to the tumor, there was an oval hypoechoic lesion about 40 mm in diameter. Computed tomography scan showed a solid, echogenic, strictly limited tumor at the fundus of the bladder, anteriorly, 32 ? 35 ? 22 mm in diameter which was positive after contrast application. The patient underwent partial cystectomy with complete excision of the tumor lesion 1.5 cm in healthy tissue. Histopathological analysis showed diagnosis of Adenocarcinoma mucinosum vesicae urinariae infiltrans. Patohistological findings detected a part of the urachal wall with a thin layer of fibromuscular tissue, chronic inflammation, microcalcifications in the lumen, flattened and desquamated epithelium. One year after the surgery, there were no signs of primary disease or metastases in other organs. Conclusion. Urachal adenocarcinoma is extremely rare. Long term survival could be achieved by surgical treatment in the early stage of the disease which consists of complete resection of urachal carcinoma and partial or total cystectomy.

Esophageal Cancer

Cancer of the esophagus is the eighth most common malignancy worldwide in terms of incident cases and the sixth most common for cancer deaths. The two main histopathologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EADC), have strikingly different clinical and epidemiologic features. ESCC occurs throughout the esophagus and is the most common histologic subtype globally; over 90% of cases in the traditionally high-risk regions of Eastern Asia and Eastern and Southern Africa are ESCC. The incidence of ESCC is decreasing worldwide. In some high-risk areas in Asia the decrease was preceded by economic development and improvements in diet, whereas in high-income countries the decrease followed reductions in cigarette smoking. In contrast, the incidence of EADC continues to increase in many high- and middle-income countries, especially among white men. EADC develops in the lower third of the esophagus, primarily because of gastroesophageal reflux disease (GERD) and obesity.