Philip Tomashefsky

The cofactor effect: varicocele and infertility *

The varicocele may be a cofactor that, when potentiated by other cofactors (i.e., gonadotoxins), causes male infertility. This hypothesis could explain the unpredictable effects of the varicocele on fertility. Male rats with experimental varicoceles, sham surgery, or no surgery were treated for 30 days with the known gonadotoxins cyclophosphamide or nicotine. Spermatogenesis was assessed by flow cytometry. Cyclophosphamide alone caused gonadotoxicity, and its effect was accentuated by sham or varicocele surgery. Nicotine and the presence of a varicocele were more gonadotoxic than either the varicocele or nicotine by itself. This data would lend support to the cofactor hypothesis of the pathophysiology of the varicocele.

Enzyme levels in the growing and spontaneously regressing Flexner-Jobling carcinoma. I. Catheptic activity and phosphatases.

Abstract In contrast to nonregressing tumors, the spontaneously regressing Flexner-Jobling carcinoma changes its enzymatic pattern in the course of regression. Catheptic activity was found to increase considerably. On the other hand, the level of alkaline phosphatase in regressing tumors is markedly decreased. There is also a tendency toward lower alkaline phosphatase levels in the first 10 days after transplantation. Alkaline phosphatase activity thus seems to go through a maximum: it is low in the first 10 days of tumor growth, it reached its highest activity after the first 10 days interval, and in the course of regression it is again reduced to low levels. The increase in catheptic activity in the course of tumor regression has been tentatively interpreted as an enzymatic equilibrium shift from protein synthesis to hydrolysis, an autolysis in vivo, concerned with the splitting and subsequent removal of the tumor proteins.

Keyhole-Limpet Haemocyanin (KLH) immunotherapy of murine transitional cell carcinoma

SummaryThe antigenicity of transitional cell carcinoma of the bladder has stimulated the search for effective immunotherapeutic agents in the treatment of this disease. Non-specific immunotherapy with local (intravesical/intralesional) and systemic Keyhole Limpet Haemocyanin (KLH) in a FANFT induced murine bladder tumor model was studied. Results showed no difference between control or treated groups in either tumor growth or animal survival.

Bone Marrow Acid Phosphatase in Prostate Cancer: An Assessment by Immunoassay and Biochemical Methods

Comparisons of the bone marrow and serum acid phosphatase values obtained by counterimmunoelectrophoresis and the Roy biochemical test were made in 72 patients with and in 13 patients without prostatic cancer. The counter-immunoelectrophoresis test, when positive at more than 1 international unit per liter, showed only 4.4% falsely positive results. The Roy biochemical test, which uses sodium thymolphthalein monophosphate as the substrate, had 65% falsely positive bone marrow acid phosphatase levels. Conflicting reports regarding the value of bone marrow acid phosphatase determinations in patients with prostatic cancer result from the use of non-specific substrates in biochemical methods for measurement and from the trauma incidental to bone marrow aspiration, which releases many non-prostatic acid phosphatase enzymes. The use of immunoassay such as counter-immunoelectrophoresis minimizes this source of error.

Role of the pituitary in growth of a transplanted rat tumor.

Summary Hypophysectomy in rats definitely, but incompletely, suppresses the growth of a transplanted tumor. It appears possible that a hormone, or hormones, of the pituitary are required for stimulation of tumor growth as evidenced by the effects of pituitary gland removal and the partial results of the administration of certain anterior pituitary extracts.

Enzyme levels in the growing and spontaneously regressing Flexner-Jobling carcinoma. II. ATPase and glycolysis☆

Abstract Glycolysis by homogenates from regressing tumors, in terms of lactic acid production, is reduced by an average of 54% as compared to homogenates from nonregressing tumors. This decrease is due to a sharp rise of the ATPase levels in the regressing tumor homogenates. Addition of fluoride, an ATPase inhibitor, will completely restore glycolysis as compared to homogenates from nonregressing tumors under identical conditions. In the presence of AMP, added either initially to the medium or produced enzymically from ATP or ADP, the lactic acid assay is higher than indicated by the CO 2 evolution from a bicarbonate-containing medium. The same is true of the phosphate assay in the incubation of ATP, MgCl 2 , and bicarbonate-phosphate with tumor homogenate. Additional evidence to that brought forth by other investigators suggests the enzymically catalyzed interaction between CO 2 and a split product of ATP.

Interaction of ultrasound with neoplastic tissue IV. Alteration of biologic activity in cells derived from rat wilms' tumor sonicated in vivo

Paired Wistar-Furth male rats were implanted subcutaneously with the Furth-Columbia rat Wilms tumor. Seven days after implantation the tumors were either subjected to therapeutic ultrasound irradiation or were left as untreated controls. On the ninth day after implantation the animals were sacrificed, and suspensions of cells were made from the excised tumors by trypsinization. The cells were counted using trypan blue dye as an indicator of viability. New rats were then implanted with cells either from sonicated tumors or cells from controls. In half the recipient animals the suspensions were matched by total cell count. In the other half of the rats cell counts were matches for viability by the dye exclusion test. Tumors developed in a total of 8 of 11 rats receiving control cells and they died. A palpable tumor did not develop in any rat receiving cells fromsonicated tumors during the ninety-day study period. Surviving rats were challenged with Wilms tumor by trocar implant. Tumor developed in all recipients, and they died.

32P-Labeled thio-tepa absorption in normal rat bladders Potential guide for intravesical chemotherapy in bladder cancer

Bladders of normal rats were used to evaluate the absorption of thio-tepa after intravesical instillation. Thio-tepa labeled with 32P (radioactive phosphorus) was utilized to measure drug concentrations in bladder wall, liver, and bone marrow. Thio-tepa was rapidly absorbed into the general circulation, and significant amounts of isotope were found. Thio-tepa absorption patterns in the normal rat may serve as a guide in adjusting drug dosages when thio-tepa is used intravesically in human beings for the treatment of superficial, papillary bladder tumors.

Alterations of physical and biochemical parameters of the R3327-CP rat prostate adenocarcinoma following hormonal manipulation of the host.

Several physical and biochemical parameters of a rapidly growing, hormonally responsive, poorly differentiated strain of Dunning R3327 rat prostatic adenocarcinoma (the CP strain) were monitored for 1 month during growth in control and hormonally manipulated male Fischer X Copenhagen rats. The tumor was implanted into control rats and into rats 1 month following orchiectomy. Twenty-nine days following tumor implantation, 1 group of unoperated rats was orchiectomized while the rats implanted subsequent to orchiectomy were repleted with pharmacological doses of testosterone. At 2 and 4 weeks following treatment, half the original number of rats from each group were sacrificed and the growth rate (doubling time), per cent of aneuploid cells and androgen receptor levels (total, cytoplasmic and nuclear) were determined for each tumor. Orchiectomy increased tumor doubling time, while testosterone repletion decreased it, demonstrating the hormonal dependence of this tumor strain. Orchiectomy also decreased the levels of aneuploid cells in the tumor; however, repletion of testosterone to rats orchiectomized prior to implantation did not restore the aneuploid cell number to control levels. A sensitive indicator of the hormonal status of the tumor was the per cent of androgen receptors in the nucleus. Tumors grown in rats orchiectomized after implantation had the lowest percentage of androgen receptor in the nucleus while orchiectomized rats repleted with testosterone had the highest percentage. Comparison of the levels of androgen receptors in the tumors from the various groups (androgen receptor per gram of tissue) unexpectedly revealed that tumors grown in the orchiectomized rats had slightly higher total receptor levels than did control tumors, while the tumors of orchiectomized rats repleted with testosterone had lower amounts than did the control tumors. In contrast to these findings, the prostates of orchiectomized rats replenished with testosterone had higher levels of total androgen receptor than did the prostates of control rats.

Seromucoid and Albumin Syntheses After Uninephrectomy and Partial Hepatectomy in the Rat

Summary After UNX, seromucoid synthesis represents an increasing proportion of total plasma protein synthesis. The increase reaches a sharp peak at 48 hr and rapidly diminishes. This pattern is distinct from those produced by either simple laparotomy or PHX. The seromucoid response is apparently not related to the renal hyperplastic response but is more likely a direct result of the UNX itself. After SO or PHX, relative albumin label drops. This is not observed for the first day after UNX. This may be the result of a transient increase in albumin synthesis. When UNX and PHX are done in the same animal, there is some inhibition of the respective hyperplasias but no interference with the expected restoration of lost tissue. This work was supported, in part, by the Susan B. Thomas Memorial Fund.