EFFECTS ON NEOPLASTIC CELLS 541 



action, this work continuing from 1947 to the present time. Mitchell (1948) 

 first used menadiol-diP (Synkayvite), on the basis of its potent antimitotic 

 and radiosensitizing actions on fibroblasts, in the treatment of clinical 

 neoplasms. In 116 patients with advanced malignant tumors it produced 

 in many cases a definite palliative improvement in conjunction with X-ir- 

 radiation; in bronchial carcinoma the life-span was increased significantly 

 and there was a palliative response in 23 of 73 other types of tumor. The 

 usual dose was 100 mg either intramuscularly or intravenously, the latter 

 being better, along with radiation therapy. Toxic effects were minimal, 

 there being some transient nausea and focal pain due to cellular edema in 

 the tumor. It was shown later that sections of the tumors from treated 

 patients exhibit areas of gross necrosis, blocked mitosis, and pycnotic 

 nuclear degeneration with some chromosomal fragmentation (Mitchell, 

 1949). The menadiol-diP treatment of patients with other than bronchial 

 carcinomas followed for 3.5 years was summarized by J. S. Mitchell (1953), 

 who stated, "The results suggest that the proportion of cases showing unex- 

 pectedly good clinical response is greater with radiotherapy combined 

 with the compound administered by intravenous injection than with radio- 

 therapy combined with the compound administered by intramuscular 

 injection." He believed it to have a small but useful effect as a radiosensiti- 

 zer. The mean survival of bronchial carcinoma cases was raised from 5.9 

 to 10.8 months when intravenous injections of menadiol-diP were used. 

 It has been claimed that menadiol-diP-2-C^* given to Walker carcinoma- 

 bearing rats is concentrated more in the tumor than in other tissues, but 

 analysis of the data shows that, although this is true for muscle, it is not 

 generally true* (Marrian and Maxwell, 1956). We may also mention the 

 recent report of Deeley (1962) confirming the results of Mitchell, mena- 

 diol-diP prolonging survival of patients with bronchial carcinoma over 

 that of patients receiving radiation alone. 



The report by Friedmann and Bailey (1950) on the treatment of rats 

 with Jensen sarcoma by intramuscular injections of 1,4-naphthohydro- 

 quinone-diP and menadiol-diP, in which it was claimed that little or no 

 effect was observed (although tumor weight fell from 22.48 to 18.73 g), 

 cannot be seriously considered as a true test of the compounds since only 

 a single dose by a rather unfavorable route was used. Mitchell's work has 

 been criticized by Gellhorn and Gagliano (1950) on the basis of a lack of 

 proper criteria for a beneficial palliative effect, and they could find no 

 suppressive effect of menadiol-diP on various transplanted tumors in ani- 

 mals; however, the substance was given intraperitoneally, which is probably 



* Many substances, particularly those with ionic groups, do not enter skeletal mus- 

 cle as readily as they do most other tissues, as has been clearly shown in much recent 

 work with drugs, so that a tumor-muscle ratio greater than unity for menadiol-diP 

 does not signify a special concentrating mechanism. 



