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View the Table of Contents for the January 15 issue of Clinical Cancer Research.
Hastings et al. Page 499
Although best known as the mediator of hypercalcemia of malignancy, parathyroid hormone-related protein (PTHrP) also modulates the malignant phenotype in many carcinomas. To evaluate its relationship with survival in non-small cell lung carcinoma (NSCLC), Hastings et al. assessed PTHrP immunoreactivity in paraffin-embedded tumor samples. Tumor PTHrP was a significant predictor of survival in females, independent of stage, histology and age, but had no relationship with survival in male patients. Exploration of this area could improve understanding of sex-related factors in the pathogenesis of lung cancer and could lead to prognostic tests and therapies involving PTHrP.
Grabert et al. Page 569
In cancer immunotherapy, limitations such as number and specificity of cytotoxic T lymphocytes may be overcome by using activated T cells (ATC) armed with bispecific antibodies to target tumor cells in vivo. Grabert et al. show that ATC bearing anti-CD3 x Her2/neu bispecific antibodies cocultured with Her2/neu+ targets were viable, divided, mediated specific cytotoxicity, and secreted both cytokines and chemokines for up to 2 weeks with repeated stimulation. Moreover, PBMC from Her2Bi-armed ATC treated-patients exhibited increased tumor cell–specific cytotoxicity. Therefore, these data suggest that armed ATC will not only kill tumor cells in vivo, but may modulate endogenous antitumor immune responses.
Yamanaka et al. Page 376
Cutaneous T-cell lymphomas (CTCL) are malignancies of skin-homing T lymphocytes that produce a Th2 cytokine profile. Most normal skin-homing CD4+ T cells produce Th1 cytokines, and the reason for the Th2 bias in CTCL is unclear. IL-18 is a cytokine that can favor the generation of Th2 T cells, particularly in the absence of IL-12. Yamanaka et al. analyzed plasma and lesional skin from CTCL patients, and found that IL-18 and its converting enzyme caspace-1 were significantly elevated. In contrast, IL-12 levels were low or absent in the same compartments. Active IL-18, therefore, may play a role in the Th2 bias seen in most types of CTCL.
Haapasalo et al. Page 473
Carbonic anhydrase IX (CA IX) is a hypoxia-inducible enzyme, which is associated with neoplastic growth. Haapasalo et al. described CA IX expression in human diffusely infiltrating astrocytomas. CA IX immunoreactivity showed strong association to tumor malignancy grades and had significant prognostic value in univariate and multivariate survival analyses. These findings suggest that CA IX is a useful biomarker for predicting poor prognosis of astrocytic tumors and may also be a promising target molecule for improvement of therapeutic interventions.
Abraham et al. Page 353
The EphA2 receptor tyrosine kinase is upregulated in several types of human cancer and restoration of EphA2-Ephrin A1 signaling has been found to decrease cancer progression. To investigate EphA2 expression in bladder cancer as a potential therapeutic target, Abraham et al. determined the expression pattern of EphA2 in cell lines and tissues from urinary bladder cancer and its relation to Ephrin A-1 and E-cadherin regulatory molecules. EphA2 expression increased in advanced stages of urinary bladder cancer. Further, adenoviral delivery of Ephrin A-1 decreased proliferation of bladder cancer cells in vitro, indicating EphA2 as a potential target in urinary bladder cancer therapy, and which is significant in the light of molecules being developed to modulate EphA2.