Dichloroacetate should be considered with platinum-based chemotherapy in hypoxic tumors rather than as a single agent in advanced non-small cell lung cancer

Objectives

Dichloroacetate (DCA) is a highly bioavailable small molecule that inhibits pyruvate dehydrogenase kinase, promoting glucose oxidation and reversing the glycolytic phenotype in preclinical cancer studies. We designed this open-label phase II trial to determine the response rate, safety, and tolerability of oral DCA in patients with metastatic breast cancer and advanced stage non-small cell lung cancer (NSCLC).

Materials and methods

This trial was conducted with DCA 6.25 mg/kg orally twice daily in previously treated stage IIIB/IV NSCLC or stage IV breast cancer. Growth inhibition by DCA was also evaluated in a panel of 54 NSCLC cell lines with and without cytotoxic chemotherapeutics (cisplatin and docetaxel) in normoxic and hypoxic conditions.

Results and conclusions

Under normoxic conditions in vitro, single-agent IC₅₀ was >2 mM for all evaluated cell lines. Synergy with cisplatin was seen in some cell lines under hypoxic conditions. In the clinical trial, after seven patients were enrolled, the study was closed based on safety concerns. The only breast cancer patient had stable disease after 8 weeks, quickly followed by progression in the brain. Two patients withdrew consent within a week of enrollment. Two patients had disease progression prior to the first scheduled scans. Within 1 week of initiating DCA, one patient died suddenly of unknown cause and one experienced a fatal pulmonary embolism. We conclude that patients with previously treated advanced NSCLC did not benefit from oral DCA. In the absence of a larger controlled trial, firm conclusions regarding the association between these adverse events and DCA are unclear. Further development of DCA should be in patients with longer life expectancy, in whom sustained therapeutic levels can be achieved, and potentially in combination with cisplatin.     

Intussusception in a child with respiratory syncytial virus: a new association

Intussusception is known to be associated with childhood viral illnesses. Respiratory syncytial virus (RSV) has not, to our knowledge, been previously reported in association with intussusception. We report a case of a 4-month-old boy admitted with RSV bronchiolitis, who subsequently developed an intussusception during the hospital course, necessitating laparotomy and resection.     

A rare case of myocardial infarction due to parathion poisoning

Organophosphorus poisoning occurs very commonly in southern India where farmers form a significant proportion of the population who commonly use organophosphorus compounds like parathion as insecticides. Awareness of the complications caused by parathion poisoning is essential for proper monitoring and treatment. We report a case of suicidal parathion poisoning in a farmer who was treated with atropine and oximes. He subsequently developed myocardial infarction, to the treatment of which, he showed no response and succumbed. In conclusion, myocardial infarction is a rare complication of parathion poisoning. Awareness of this complication of parathion poisoning, proper monitoring and treatment could prevent fatalities.     

Expression of cellular oncogenes during embryonic and fetal development of the mouse.

Cellular oncogenes are conserved with great fidelity across a broad span of evolution. This avid conservation suggests possible roles in critical physiologic functions. Little, however, is known about their activity in normal cellular processes. In this study, we examined the expression pattern of eight cellular oncogenes during embryonic and fetal development of the mouse. Five of these genes (c-myc, c-erb, c-Ha-ras, c-src, and c-sis) were expressed at appreciable levels, and four were modulated in a consistent manner during the course of prenatal development.     

Paraneoplastic vasculitis associated with multiple myeloma

The association between vasculitis and cancer has been widely reviewed in recent decades. The existence of malignancies in patients with vasculitis has been estimated at about 4.5-8%, haematological neoplasms being the most frequently observed. The haematological malignancies most frequently described are lymphoproliferative diseases such as hairy cell leukaemia and lymphomas. On the contrary, the incidence of paraneoplastic vasculitis in patients with myeloma is low; up to now, we have found nine cases reported on this subject. We report the case of a 73-year-old woman who in 1 year showed three outbreaks of acutely painful, purpuric and ulceronecrotic lesions, localized on the lower extremities. Histopathological study demonstrated thrombosis in the arterioles and leucocytoclastic vasculitis. Complementary tests revealed the presence of multiple myeloma.