Gastric cancer mesenchymal stem cells promote tumor glycolysis and chemoresistance by regulating B7H3 in gastric cancer cells.

Despite surgical treatment combined with multidrug therapy having made some progress, chemotherapy resistance is the main cause of recurrence and death of gastric cancer (GC). Gastric cancer mesenchymal stem cells (GCMSCs) have been reported to be correlated with the limited efficacy of chemotherapy in GC, but the mechanism of GCMSCs regulating GC resistance needs to be further studied. The gene set enrichment analysis (GSEA) was performed to explore the glycolysis-related pathways heterogeneity across different cell subpopulations. Glucose uptake and lactate production assays were used to evaluate the importance of B7H3 expression in GCMSCs-treated GC cells. The therapeutic efficacy of oxaliplatin (OXA) and paclitaxel (PTX) was determined using CCK-8 and colony formation assays. Signaling pathways altered by GCMSCs-CM were revealed by immunoblotting. The expression of TNF-α in GCMSCs and bone marrow mesenchymal stem cells (BMMSCs) was detected by western blot analysis and qPCR. Our results showed that the OXA and PTX resistance of GC cells were significantly enhanced in the GCMSCs-CM treated GC cells. Acquired OXA and PTX resistance was characterized by increased cell viability for OXA and PTX, the formation of cell colonies, and decreased levels of cell apoptosis, which were accompanied by reduced levels of cleaved caspase-3 and Bax expression, and increased levels of Bcl-2, HK2, MDR1, and B7H3 expression. Blocking TNF-α in GCMSCs-CM, B7H3 knockdown or the use of 2-DG, a key enzyme inhibitor of glycolysis in GC cells suppressed the OXA and PTX resistance of GC cells that had been treated with GCMSCs-CM. This study shows that GCMSCs-CM derived TNF-α could upregulate the expression of B7H3 of GC cells to promote tumor chemoresistance. Our results provide a new basis for the treatment of GC.

Spontaneous gastric carcinomas in sooty mangabeys (Cercocebus atys).

Sooty mangabeys (Cercocebus atys) are native to West Africa and are a natural host of SIV, which is implicated in the origin of HIV2. They have been used in studies of AIDS pathogenesis, leprosy, immune responses, reproductive biology, and behavior. Spontaneous tumors have rarely been reported in this species. However, we noted spontaneous gastric carcinomas in 8 sooty mangabeys. Four male and 4 female mangabeys had mild to severe chronic weight loss, with abdominal distention in 5 of 8 animals. At necropsy, 7 of the 8 mangabeys had prominent large ulcerated masses with severe, diffuse thickening of the pyloric wall at or near the gastric-duodenal junction, which often partially occluded the gastric lumen. Early carcinoma was an incidental finding in one mangabey. Histologically, all of the tumors were classified as adenocarcinomas. Adenocarcinomas were noncircumscribed with infiltrates of neoplastic epithelial cells, often arranged in acini. In 3 mangabeys, these infiltrates were transmural and invaded surrounding tissue locally. The adenocarcinomas were locally invasive, with metastasis to regional lymph nodes in 2 animals, but widespread metastasis was not seen. Anisocytosis, anisokaryosis, and high mitotic rates were seen in all 8 tumors. In the samples available, serology and Steiner stain did not detect Helicobacter, and immunohistochemistry failed to reveal Helicobacter or Epstein-Barr virus, 2 potential causes for human gastric carcinomas.

Florid cutaneous papillomatosis with adenocarcinoma of stomach in a 35 year old male.

Various paraneoplastic dermatoses may be seen in association with underlying visceral, especially gastrointestinal, malignancy. Florid cutaneous papillomatosis describes the sudden appearance of multiple acuminate keratotic papules that morphologically resemble viral warts. It may be seen in association with acanthosis nigricans and/or the sign of Leser Triotalat. We report a 35-year-old male with extensive seborrhoeic keratoses and florid cutaneous papillomatosis. Unusually marked verrucous changes caused disfigurement of the hands and feet. The patient also reported dyspepsia, abdominal distention and weight loss 6 months prior to the development of cutaneous lesions. Gastroscopy revealed a large growth in the stomach. Histopathology of the tumor showed features of adenocarcinoma.

Malignant acanthosis nigricans with liver secondaries from an occult primary adenocarcinoma of gastrointestinal tract.

A 38-year-old female presented with hyperpigmented velvety plaques on the nape and the sides of the neck with diffuse pigmentation of the face and flexures suggestive of acanthosis nigricans. The dorsa of both the hands showed increased rugosity, hyperpigmentation and hyperkeratosis of the palms, suggestive of tripe palms. Investigations revealed multiple secondaries in the liver. Histopathology showed the secondaries to be from adenocarcinoma of the gastrointestinal tract.

[Clinico-pathological findings of gastrointestinal tract in the leprosy patients].

Endoscopic biopsies either or both for the stomach and colon looking for chronic gastritis and carcinomata followed by the histopathologic examinations of the mucosa were applied to long term leprosy inpatients and controls. 1) In chronic gastritis, glandular atrophy with cellular infiltration and submucosal fibrosis likewise intestinal metaplasia were predominated in the leprosy patients, in the comparison of the cases consisted of 30 leprosy patients and 16 controls. No characteristic changes for leprosy cases were encountered accordingly, however, as the sequences of the medications. 2) The observations of Helicobacter pylori (HP) by means of immunohistologic method were also applied to gastritic cases. However, the positive rates in the above groups were not much different one another. 3) The cases of gastric carcinoma were 14 during 14 years period, among which 9 showed protruded lesions indicating metaplastic changes as the precancerous lesion. 4) The carcinoma of the colon tended to be left sided in the leprosy patients.

Leprosy and malignancy: autopsy findings of 252 leprosy patients.

The occurrence of malignant tumors in leprosy patients was studied in 252 autopsied cases. Malignant tumors were found in 33 out of 110 autopsy cases from 1962 to 1971, and in 51 out of 141 autopsy cases from 1977 to 1989 (until July). In 1974, a lepromatous case with Kaposi's sarcoma was autopsied. The incidence of malignant tumors in our 252 cases were 33.7% (85 out of 252). Carcinoma of the alimentary system was most common: stomach, liver and large intestine, in that order. There was an increased number of hepatocellular carcinoma closely related to liver cirrhosis. Carcinoma of the lung has increased remarkably in leprosy patients quite recently. Malignant lymphoma was the most common of the nonepithelial malignant tumors, and four of these cases were seen in lepromatous leprosy patients. Eight cases showed double or triple cancers; seven of these were autopsied during 1977 to 1989. Further studies should be done to ascertain which types of leprosy showed the highest incidence, and which sex showed more frequent malignant tumors.