oxalates and Lung-Neoplasms

Nowadays cisplatin doublets are considered the gold-standard treatment in advanced non-small cell lung cancer (NSCLC) patients, but are often associated to poor toxicity profile. In the last years different schedules have been developed in order to improve the tolerability of these regimens. Carboplatin is gradually replacing cisplatin in clinical practice as well as in clinical trials even if it is still unclear whether it has an equivalent efficacy compared to cisplatin. Oxaliplatin, the trans-l oxalato platinum compound, showed encouraging antineoplastic activity and favourable toxicity profile in NSCLC, but confirmatory randomized phase III trials are warranted. We performed a literature search in order to better understand the possible role of oxaliplatin-based combinations in advanced NSCLC treatment strategies.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cisplatin; Clinical Trials, Phase III as Topic; Disease Progression; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Oxalates; Randomized Controlled Trials as Topic; Survival Analysis; Taxoids; Treatment Outcome

Estrogen therapy has used to prevent bone loss in postmenopausal women. Although therapeutically enhanced estrogen levels have been suggested, patients are exposed to greater risks of nephrolithiasis and cancer. It has been known that oxalate or bicarbonate transporter SLC26A6 is involved in oxalate homeostasis and its deletion results in kidney stone formation and addressed that patients with kidney stones possess higher cancer risk. Thus, the mechanism of the interaction between estrogen and SLC26A6 and the effect of SLC26A6 on cancer cells should be elucidated. In this study, we investigated whether β-estradiol treatment modulates SLC26A6 expression and its bicarbonate or oxalate transporting activity and affects the proliferative and migratory ability of A549 cells. The β-estradiol stimulation attenuated oxalate or bicarbonate transporting activities through SLC26A6. Knockdown of SLC26A6 reduced transporter activity whereas enhanced cellular migration. β-estradiol-mediated cellular migration was independent of SLC26A6 transporter activity, whereas enhanced SLC26A6 expression attenuated cellular migration even in the presence of β-estradiol treatment. These results indicate β-estradiol treatment enhances cancer cell migration and dysregulates oxalate transport by inhibiting SLC26A6 activity, suggesting reduced oxalate transporting activity may involve in the oxalate homeostasis.

Topics: Antiporters; Bicarbonates; Estradiol; Estrogens; Female; Humans; Lung Neoplasms; Oxalates; Sulfate Transporters

Metabolic reprogramming has been shown to be involved in cancer-induced pre-metastatic niche (PMN) formation, but the underlying mechanisms have been insufficiently explored. Here, we showed that hydroxyacid oxidase 1 (HAO1), a rate-limiting enzyme of oxalate synthesis, was upregulated in the alveolar epithelial cells of mice bearing metastatic breast cancer cells at the pre-metastatic stage, leading to oxalate accumulation in lung tissue. Lung oxalate accumulation induced neutrophil extracellular trap (NET) formation by activating NADPH oxidase, which facilitated the formation of pre-metastatic niche. In addition, lung oxalate accumulation promoted the proliferation of metastatic cancer cells by activating the MAPK signaling pathway. Pharmacologic inhibition of HAO1 could effectively suppress the lung oxalate accumulation induced by primary cancer, consequently dampening lung metastasis of breast cancer. Breast cancer cells induced HAO1 expression and oxalate accumulation in alveolar epithelial cells by activating TLR3-IRF3 signaling. Collectively, these findings underscore the role of HAO1-mediated oxalate metabolism in cancer-induced lung PMN formation and metastasis. HAO1 could be an appealing therapeutic target for preventing lung metastasis of cancer.

Topics: Alcohol Oxidoreductases; Animals; Extracellular Traps; Lung; Lung Neoplasms; Mice; Oxalates

Melanoma is the most aggressive skin cancer due to a high propensity for metastasis, with a 10-year survival rate of less than 10%. The devastating clinical outcome and lack of effective preventative therapeutics for metastatic melanoma necessitate the development of new therapeutic strategies targeted to inhibit the regulatory circuits underlying the progression and metastasis of melanoma. Melanoma metastasis requires migration and invasion of the malignant tumour cells driven by proteolytic remodelling of the extracellular matrix (ECM) executed by matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9. Inhibiting components of these circuits defines new therapeutic opportunities for melanoma with metastatic malignancy. Oxalomalate (OMA) is a competitive inhibitor of NADP

Topics: Animals; Cell Movement; Isocitrate Dehydrogenase; Lung Neoplasms; Male; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Oxalates; Oxidative Stress; Reactive Oxygen Species; Signal Transduction

Topics: Aerosols; Animals; Autoradiography; Bone and Bones; Dose-Response Relationship, Radiation; Female; Femur; Injections, Intravenous; Lung; Lung Neoplasms; Male; Neoplasms, Radiation-Induced; Neptunium; Nitrates; Osteosarcoma; Oxalates; Radiation Effects; Rats; Sex Factors