One-year mortality and consequences of COVID-19 in cancer patients: A cohort study.

The 1-year mortality and health consequences of COVID-19 in cancer patients are relatively underexplored. In this multicenter cohort study, 166 COVID-19 patients with cancer were compared with 498 non-cancer COVID-19 patients and 498 non-COVID cancer patients. The 1-year all-cause mortality and hospital mortality rates in Cancer COVID-19 Cohort (30% and 20%) were significantly higher than those in COVID-19 Cohort (9% and 8%, both P < .001) and Cancer Cohort (16% and 2%, both P < 0.001). The 12-month all-cause post-discharge mortality rate in survival discharged Cancer COVID-19 Cohort (8%) was higher than that in COVID-19 Cohort (0.4%, P < .001) but similar to that in Cancer Cohort (15%, P = .084). The incidence of sequelae in Cancer COVID-19 Cohort (23%, 26/114) is similar to that in COVID-19 Cohort (30%, 130/432, P = .13). The 1-year all-cause mortality was high among patients with hematologic malignancies (59%), followed by those who have nasopharyngeal, brain, and skin tumors (45%), digestive system neoplasm (43%), and lung cancers (32%). The rate was moderate among patients with genitourinary (14%), female genital (13%), breast (11%), and thyroid tumors (0). COVID-19 patients with cancer showed a high rate of in-hospital mortality and 1-year all-cause mortality, but the 12-month all-cause post-discharge mortality rate in survival discharged cancer COVID-19 patients was similar to that in Cancer Cohort. Comparing to COVID-19 Cohort, risk stratification showed that hematologic, nasopharyngeal, brain, digestive system, and lung tumors were high risk (44% vs 9%, P < 0.001), while genitourinary, female genital, breast, and thyroid tumors had moderate risk (10% vs 9%, P = .85) in COVID-19 Cancer Cohort. Different tumor subtypes had different effects on COVID-19. But if cancer patients with COVID-19 manage to survive their COVID-19 infections, then long-term mortality appears to be similar to the cancer patients without COVID-19, and their long-term clinical sequelae were similar to the COVID-19 patients without cancer.

[The inhibitory effect of tranilast on transforming growth factor-beta(2) expression in cultured human trabecular meshwork cells].

OBJECTIVE: To investigate the effect of tranilast on transforming growth factor-beta(2) (TGF-beta(2)) expression in cultured human trabecular meshwork cells. METHODS: TGF-beta(2) expression in cultured 3-5 passage human trabecular meshwork cells was measured by semi-quantitative RT-PCR after treated with 0.0 micro g/ml (control), 12.5, 25.0 and 50.0 mg/L tranilast for 48 h. RESULTS: The value of TGF-beta(2)/G3PDH of cells treated with 12.5, 25.0 and 50.0 mg/L tranilast was 1.85 +/- 0.35, 1.66 +/- 0.42, 1.16 +/- 0.24, respectively. The difference between these treated groups and that of the control group (3.82 +/- 0.56) was statistically significant (q' = 10.77, 11.80, 14.54, P < 0.01), respectively. The value of TGF-beta(2)/G3PDH in the tranilast treated trabecular meshwork cells decreased in a dose-dependent manner. CONCLUSION: Tranilast could inhibit TGF-beta(2) expression in cultured human trabecular meshwork cells. It is worth to study the using of tranilast in the treatment of primary open-angle glaucoma.

Apoptosis of human trabecular meshwork cells induced by transforming growth factor-beta2 in vitro.

Whether transforming growth factor-beta2 (TGF-beta2) induces apoptosis of human trabecular meshwork cells was investigated in vitro. Cultured 3-5 passage human trabecular meshwork cells were treated with 0 (control), 0.32, 1, 3.2 ng/ml TGF-beta2 for 48 h and divided into control group and experimental group. The apoptosis of human trabecular meshwork cells was examined by transmission electron microscopy, TUNEL technique and flow cytometry. The results showed characteristic morphologic changes of apoptotic cells were observed under transmission electron microscopy. DNA fragmentation of human trabecular meshwork cells was found by TUNEL technique. Quantitative analysis of flow cytometry showed that percentages of apoptotic human trabecular meshwork cells were (2.79 +/- 0.44)%, (4.43 +/- 1.17)% and (9.60 +/- 2.05)% respectively with different concentrations [1 ng/ml (P<0.05), 3.2 ng/ml (P<0.01)] of TGF-beta2 with the difference being significant between experimental group and control group [(1.41 +/- 0.34)%]. It was concluded that TGF-beta2 can induce apoptosis of human trabecular meshwork cells in vitro and may be involved in the decrease of trabecular meshwork cells in the patients with primary open angle glaucoma and aging of normal people.

Antagonistic effects of tranilast on proliferation and collagen synthesis induced by TGF-beta2 in cultured human trabecular meshwork cells.

Whether tranilast had antagonistic effect on proliferation inhibition and collagen synthesis promotion induced by TGF-beta2 in cultured human trabecular meshwork cells was investigated. Suspension of 1 x 10(4) cultured human trabecular meshwork cells of 3-5 passage was distributed in each well of a 96-well disk and divided into control group and experimental group. After 24 h, 0 microg/ml (control), 12.5 microg/ml, 25 microg/ml, 50 microg/ml tranilast with 3.2 ng/ml TGF-beta2 were added into the incubation medium. Another 24 h later, proliferation and collagen synthesis in cultured human trabecular meshwork cells were examined respectively by using tetrazolium-based semiautomated colormetric (MTT) assay and 3H-proline incorporation with liquid scintillation technique. The results showed absorbance (A) values of the experimental groups were 0.9036 +/- 0.3017, 1.1361 +/-0.1352, 1.2457 +/- 0.1524 according to the different concentrations of tranilast, and 0.8956 +/-0.1903 of the control group. In comparison with the control group, 25 microg/ml (q'= 3.23, P< 0.05), 50 microg/ml (q'=4.70, P<0.01) tranilast significantly antagonized the decrease of the A values induced by TGF-beta2 in the cultured human trabecular meshwork cells. In comparison with the control group [817.37+/-124.21 cpm/10(4) cells], 12.5 microg/ml (620.33+/-80.46 cpm/10(4) cells, q'= 4.26, P<0.05), 25 microg/ml (594.58+/-88.13 cpm/10(4) cells, q'=4.81, P<0.01), 50 microg/ml (418.64+/-67.90 cpm/10(4) cells, q'=8.62, P<0.01) tranilast significantly inhibited the incorporation of 3H-proline into the cultured human trabecular meshwork cells promoted by TGF-beta2 in a dose-dependent manner. It was concluded that tranilast had the antagonistic effect on the proliferation inhibition and collagen synthesis promotion induced by TGF-alpha2 in the cultured human trabecular meshwork cells.

Effect of transforming growth factor-beta(2) on extracellular matrix synthesis in bovine trabecular meshwork cells.

OBJECTIVE: To investigate the effect of transforming growth factor-beta(2) (TGF-beta(2)) in human aqueous humor on extracellular matrix synthesis in cultured bovine trabecular meshwork cells. METHODS: Cultured 3-5 passage bovine trabecular meshwork cells were divided into control group and experimental group. After treated with 0 ng/L (control), 0.32 x 10(3) ng/L, 1.00 x 10(3) ng/L, 3.20 x 10(3) ng/L TGF-beta(2) for 48 h, collagen, fibronectin and hyaluronic acid synthesis in bovine trabecular meshwork cells were examined respectively by (3)H-proline incorportion and liquid scintillation technique, enzyme linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). RESULTS: In comparison with the control group, TGF-beta(2) significantly promoted the synthesis of collagen at 0.32 x 10(3) ng/L (P < 0.05), 1.00 x 10(3) ng/L (P < 0.01), 3.20 x 10(3) ng/L (P < 0.01), (3)H-proline incorporation increased in a concentration-dependent manner; and 1.00 x 10(3) ng/L (P < 0.05), 3.20 x 10(3) ng/L (P < 0.01) TGF-beta(2) significantly promoted the synthesis of fibronectin in cultured bovine trabecular meshwork cells. 1.00 x 10(3) ng/L (P < 0.01) and 3.20 x 10(3) ng/L (P < 0.01) TGF-beta(2) significantly inhibited the synthesis of hyaluronic acid in the cultured cells. CONCLUSION: The data suggest that TGF-beta(2) play important roles in extracellular matrix age-related changes of normal trabecular meshwork and abnormal deposition of the extracellular matrix in the trabecular meshwork, especially the juxtacanalicular tissue of primary open-angle glaucoma patients.

Insulin-like growth factor-I gene cloning and protein expression in bovine trabecular meshwork tissue and cells.

Whether cultured bovine trabecular meshwork cells and trabecular tissue ex vivo express insulin-like growth factor-I (IGF-I) messenger RNA (mRNA) and protein was investigated. Total RNA of cultured bovine trabecular meshwork cells as well as trabecular meshwork tissue freshly excised from bovine eyes was extracted, and reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect IGF-I mRNA. RT-PCR product was verified by sequencing. Immunohistochemical stain was used to detect IGF-I protein. The results showed that a single PCR amplified product was obtained, and the sequence was homologous to the known sequence.. IGF-I immunostain was positive in the cytoplasm of trabecular meshwork cells. It was concluded that trabecular meshwork cells produce IGF-I and contribute to the presence of IGF-I in trabecular meshwork microenvironment as well as aqueous humor. Trabecular meshwork cells were affected by IGF-I not only through paracrine, but also autocrine action. Whether abnormal down-regulations in IGF-I production may contribute to the pathogenesis of primary open-angle glaucoma and the possibility of promoting the autocrine action of IGF-I by trabecular meshwork cells to treat the disease is worth further investigation.