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The specific role of C5a in cancer, especially in melanoma, has yet to be determined. Differential effects of C5a could be cancer specific. In the host defense system, C5a functions to protect the body from harmful entities via a plethora of mechanisms. Yet, C5a may also serve to potentiate cancerous process. C5a facilitates cellular proliferation and regeneration by attracting myeloid-derived suppressor cells and supporting tumor promotion. In this article, we critically reviewed the properties, mechanisms of action and functions of C5a, with particular emphasis on cancer inhibition and promotion, and clinical application of such knowledge in better management of patients with cancer. Outstanding questions and future directions in regard to the function of C5a in melanoma and other cancers are discussed.

This phase 1/2 study was the first to evaluate the safety and efficacy of the cyclin-dependent kinase (CDK) 4/6-specific inhibitor palbociclib (PD-0332991) in sequential combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. The recommended phase 2 dose was palbociclib 100 mg orally once daily on days 1-12 of a 21-day cycle with bortezomib 1.0 mg/m2 (intravenous) and dexamethasone 20 mg (orally 30 min pre-bortezomib dosing) on days 8 and 11 (early G1 arrest) and days 15 and 18 (cell cycle resumed). Dose-limiting toxicities were primarily cytopenias; most other treatment-related adverse events were grade≤3. At a bortezomib dose lower than that in other combination therapy studies, antitumor activity was observed (phase 1). In phase 2, objective responses were achieved in 5 (20%) patients; 11 (44%) achieved stable disease. Biomarker and pharmacodynamic assessments demonstrated that palbociclib inhibited CDK4/6 and the cell cycle initially in most patients.

A novel method to improve targeting and presentation of poorly immunogenic tumor-related antigens was investigated. This was performed with a molecular adjuvant constructed by covalently linking a response selective peptide agonist of C5a (YSFKDMP(MeL)aR) to known melanoma tumor-related antigens. C57Bl/6J mice were injected subcutaneously with bone marrow derived dendritic cells (DCs) pulsed with a melanoma epitope (TRP2-P2/Agonist), melanoma epitope tyrosinase (TYR/Agonist), a nonfunctional reverse conformation C5a agonist bound to TYR(reverse peptide) or DMSO-PBS vehicle. Mice were injected with the pulsed DCs and cytokines IL-2 and GMCSF three times prior to subcutaneous challenge with B16-F10 melanoma cells. All groups subsequently received DC vaccine boosters twice per week. Tumor growth was reduced and survival enhanced in mice immunized with the combination of TRP2-P2/Agonist and TYR/Agonist compared to mice receiving reverse peptide or vehicle.

Hodgkin's disease affecting the central nervous system is infrequent. Multiple lumbar punctures are sometimes required for cytological diagnosis. In this case fluoroscopy-guided cisternal puncture and routine lumbar punctures were used to obtain cerebrospinal fluid (CSF) samples for cytological analysis. Reed-Sternberg cells were observed on the CSF sample obtained through the cisternal puncture while none were seen in the samples obtained with routine lumbar punctures. Without cytology, the diagnosis of meningeal carcinomatosis remains elusive. In conclusion, cisternal punctures should be entertained early in the evaluation for meningeal carcinomatosis, particularly if lumbar punctures have been unsuccessful.

Twenty-two patients with malignant lymphoma were treated with three different COP-BLAM infusional chemotherapy protocols at the Jersey Shore Medical Center. The treatment group included 18 patients with large-cell lymphoma, 3 patients with Hodgkin's disease, and 1 patient with composite lymphoma (large-cell lymphoma and Hodgkin's disease). Three patients were treated with COP-BLAM III, 9 with COP-BLAM IV, and 10 with COP-BLAM V. The age of the patients at diagnosis ranged from 18 to 74 years, with a median age of 64 years. One patient had stage I bulky disease, 4 had stage II bulky disease, 3 had stage III disease, and 14 had stage IV disease. Twenty patients were evaluable for response; 2 were too early to evaluate. Complete response (CR) was seen in 18 of the 20 evaluable patients (90%). Potential cure (excludes non-lymphoma-related deaths) at 24 months is projected at 78%. Eleven patients are presently without disease and off therapy (55%). Projected failure-free survival at 2 years is 71% (a failure being death from any cause). Eleven of 22 patients developed 15 febrile episodes. Vincristine neuropathy was seen in 6 patients. Subclinical pulmonary fibrosis was seen in 1 patient. There was one cardiotoxic death. The COP-BLAM infusional protocols are highly effective, tolerable regiments that are applicable in community hospitals and can yield good response rates, with a high percentage of disease-free survivors in all age groups. The treatment can be completed in a short period with acceptable toxicity.