G-protein signaling modulator 1 promotes colorectal cancer metastasis by PI3K/AKT/mTOR signaling and autophagy.

BACKGROUND: Colorectal cancer is the second most common malignant tumor worldwide. A deeper insight into the mechanisms underlying colorectal cancer metastasis is urgently needed. G-protein signaling modulator 1 and autophagy play critical roles in tumor migration and invasion. However, the biological functions and regulatory networks of G-protein signaling modulator 1 and autophagy have not yet been fully studied. METHODS: We performed immunohistochemistry and clinic-pathological characteristic analysis in 328 human colorectal cancer specimens to identify the clinical role of G-protein signaling modulator 1 in colorectal cancer. An in vitro coculture system and a tumor metastasis mouse model were used to explore the biological function of G-protein signaling modulator 1 on tumor metastasis. Autophagic flux detection like GFP-LC3B signal immunofluorescence and electron microscope observation of autophagic vesicles and confocal microscope detection were used to gain insights into the underlying role of G-protein signaling modulator 1 in autophagy. RESULTS: We found that G-protein signaling modulator 1 was abundantly expressed in colorectal cancer tissues and was associated with lymph node metastasis and poor prognosis. Furthermore, our bioinformatic and functional studies demonstrated that G-protein signaling modulator 1 significantly promoted cell migration and invasion, both in vitro and in vivo. Mechanistically, we demonstrated that G-protein signaling modulator 1 could promote colorectal cancer cell migration and invasion and inhibit autophagy and by activating the PI3K/AKT/mTOR pathway. CONCLUSIONS: We proposed that G-protein signaling modulator 1 promotes colorectal cancer metastasis by modulating autophagy through the PI3K/AKT/mTOR pathway.

Renal cell carcinoma in patients with end-stage renal disease: a clinicopathological analysis / 中华病理学杂志

Objective@#To investigate the clinicopathological characteristics and prognosis of renal cell carcinoma (RCC) in patients with end-stage renal disease (ESRD).@*Methods@#The clinicopathological data of patients of renal cell carcinoma arising in end-stage renal disease were collected from the Affiliated Hospital of Qingdao University (ten cases) and 971 Hospital of PLA Navy (five cases) from January 2009 to August 2018.@*Results@#Among 15 patients, 14 were male and 1 was female, and the age ranged from 38 to 78 years (mean 51 years, median 49 years). All patients had history of chronic renal failure (7-192 months), including 9 patients treated with hemodialysis for 6 to 132 months. In 12 cases the tumor border was distinct and the tumor size ranged from 1.8 to 11.0 cm. Two cases were multifocal and one case showed extensive renal hemorrhage with an inconspicuous tumor mass. Microscopically, 9 cases were clear cell reanl cell carcinoma including one with sarcomatoid differentiation, 4 were acquired cystic kidney disease-associated(ACKD-RCC) and two were papillary renal cell carcinoma. All patients had a follow-up of 3 to 120 months. Four patients died during a follow-up of 6 to 60 months (mean 30 months) as a result of extensive distant metastases (two cases) and renal failure (two cases), while other eleven patients were alive without tumor recurrence or metastasis (median 40.8 months of follow-up ranging from 3 to 120 months).@*Conclusions@#ESRD-RCC is more often seen in younger male patients. The time intervals from the onset of chronic renal failure to the diagnosis of renal cell carcinoma differ and tumors are frequently incidental findings. The histological types can be sporadic renal cell carcinoma or unique ACKD-RCC. Tumors are often hemorrhagic and necrotic. Routine physical examination and early detection could benefit ESRD-RCC patients. ESRD-RCC may have a favorable prognosis despite of a large tumor size or the presence of sarcomatoid differentiation.

Clinicopathological features of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract: a report of five cases / 中华病理学杂志

Objective@#To investigate the clinicopathological features of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract.@*Methods@#Five cases of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract from the Affiliated Hospital of Qingdao University from 2016 to 2019 were retrospectively reviewed. The clinical and pathological parameters were analyzed by combining clinical data and reviewing the available literature of 35 cases (34 cases abroad and 1 case in China).@*Results@#There were 4 males and 1 female with a median age of 47 years (18-66 years). All patients had abdominal pain and constitutional symptoms including diarrhea, emaciation, intermittent mucous stool or oral and epiglottic ulcers. Endoscopic manifestations included multiple punctate congestion, erosion and ulcer at the terminal ileum and colorectum. Two cases had congestion and erosion of antrum and angle of stomach, and the lesions did not fuse and form tumors. Histologically, the lamina propria was expanded by a dense, medium to small lymphocyte infiltration, which was monomorphic, with slightly irregular nuclei without prominent nucleolus or lymphoepithelial lesions. There were admixed small amount of plasma cells and eosinophils. In 4 cases, immunohistochemistry showed the lesional cells were positive for CD3, CD8, TIA1, and negative for CD4, CD56, granzyme B and Ki-67 index was ≤10%. In situ hybridization showed that EBER was negative and clonal TCR gene rearrangement was detected. One consultation case was CD3+, CD5- and Ki-67 index of 10%, although other indicators were not done. All five patients were treated with symptomatic support. In follow-up observation for 2 to 25 months, all patients were alive with the disease.@*Conclusions@#Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract is a newly classified monoclonal T-cell proliferative disease, with low incidence, clinical inertia and long-term survival. It has unique clinicopathological features but pathologically it is easily misdiagnosed as inflammatory bowel disease or T-cell lymphoma. Correct diagnosis is of great important clinical significance.