Absolute and relative activities of platinum-complexes on human tumors as evaluated by an antimetabolic in vitro assay

An in vitro assay, which evaluates drug effect on ³H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activities were generally observed for DDP and CHIP, whereas CBDCA exhibited a lower, although not significantly different cytotoxicity on breast and ovarian cancers. The relative activities of Platinum analogues were analyzed on 239 two-way drug sensitivity comparisons. The overall agreement rates ranged from 80.2 to 83.9% for the different comparisons. High coresistance, from 61.1 to 93.8%, was observed for all the comparisons, regardless of the tumor type. Cosensitivity rates were poor for breast and ovarian cancers, from 0 to 37.5%, whereas for melanomas an association in sensitivity was observed in 80% of the cases.     

Cellular expression and genetic control of ABH antigens in primary sensory neurons of marmoset, baboon and man

ABH antigens have been demonstrated in the posterior root ganglia (PRG) of 3 primate species (marmoset, baboon and man). Their expression corresponded to the ABO phenotype of the individual and was independent of the secretor gene. In marmosets more cells were positive for H (33 +/- 9%) than for A (19 +/- 6%). In baboons A or B antigens were more easily detected (66 +/- 9%) than the H antigens (48 +/- 5%). In humans more than two-thirds of PRG cells were positive for H but only a small proportion of these were positive for A or B. The ABH antigens were found mainly in the small and intermediate-size neurons whose central processes project to lamina II of the spinal cord posterior horn. Unipolar neurons of the Gasserian ganglion, neurons of the mesencephalic nucleus of the trigeminal nerve and of some visceral ganglia have also been shown to express these antigens which are also present in the fibre layer and glomeruli of the olfactory bulbs.     

Genomic allelotyping for distinction of recurrent and de novo hepatocellular carcinoma after orthotopic liver transplantation.

Distinction between recurrent and de novo hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) bears important clinical and therapeutic implications. Techniques for molecular profiling of clinically suspected de novo and recurrent HCC are required since the histological/clinical discrimination of donor vs. recipient tumor origin is difficult. Multiple PCR amplification of 16 highly polymorphic short tandem repeat (STR) DNA sequences (routinely used for paternity and forensic assays) was applied in two patients who developed a second HCC after OLT. In both patients the technique provided reliable evidence that the two second HCC were recurrences of the primary tumor. Multiple STR genetic allelotyping is an effective tool for clear-cut discrimination of donor/recipient origin of a second HCC after OLT. Its application could be of great therapeutic relevance for such OLT patients.     

Modulation by lonidamine on the combined activity of cisplatin and epidoxorubicin in human breast cancer cells

The ability of lonidamine (LND), an energolytic derivativeof indazole-carboxylic acid, to modulate the cytotoxic activityof cisplatin (CDDP) and epidoxorubicin (EPI), singly orin combination, was investigated in two human breastcancer cell lines (MCF7 and T47D). A 72-hrpost-incubation with a non-cytotoxic concentration of LND (75M) increased the activity of a 1-hr CDDPtreatment as well as that of a 1to 16-hr EPI treatment. A different pattern ofinteraction among the drugs and modulator was observedas a function of the sequence of drugtreatment. Specifically, supra-additive or additive effects of thecombination were obtained in the two cell linesaccording to the different treatment schemes. In particular,the maximum potentiation was observed in MCF7 cellssimultaneously exposed to CDDP, EPI and LND for1 hr and then post-incubated with LND for72 hr, and in T47 first exposed toEPI and LND, then to CDDP and LND,and finally post-incubated with LND. Flow cytometric analysisof MCF7 cell distribution in the different cyclephases showed that combined treatment with EPI/CDDP/LND wasable to stabilize cell cycle perturbations (mainly G₂Maccumulation) induced by individual agents. The ability ofLND to potentiate CDDP and EPI cytotoxicity, andthe consideration that LND causes side effects differentfrom those caused by alkylating agents and anthracyclines,make this compound an attractive candidate for multidrugcombination therapy in breast cancer.     

Spontaneous Splenic Rupture in a Patient with Acute Lymphoblastic Leukemia of Burkitt Type

We describe a case of spontaneous splenic rupture occurred in a patient with acute lymphoblastic leukemia of Burkitt type before starting cytotoxic chemotherapy. Left hypochondrial pain radiating to the homolateral shoulder was the only clinical symptom. Emergency computed tomography showed splenic laceration and hemoperitoneum. The patient underwent immediate laparotomy with splenectomy and experienced an uneventful postoperative recovery. Eight days after surgery, chemotherapy could be administered and complete remission was achieved. Although spontaneous rupture of the spleen is rare in leukemia and related disorders, this diagnosis should be taken in account also when clinical symptoms are mild. Following immediate operative management, patients may completely recover and receive cytotoxic chemotherapy with substantial possibilities of achieving complete remission.