Ciência e terapia do câncer

Objective: To study the utility of Bartl ́s histological grade and staging in the prognostication of multiple myeloma.Methods: It was both a retrospective and prospective study done using all the cases of multiple myeloma from January 2001 to December 2002 with 2 years follow up. These cases were studied with special reference to Plasma cell morphology, biopsy growth pattern and tumor burden. In addition the effects of chemotherapy on post therapy marrow were also studied.

Results: During this period we studied 40 cases, of which 34 cases were Marschalko type, 6 cases Plasmablastic. The volume of infi ltration, 29 cases showed > 50% of volume of infi ltration, 3 cases showed 20-50% of volume of infi ltration and 8 cases showed <20% of volume of infi ltration. In the Pattern of involvement, Interstitial+Nodular type of involvement was commonly noted in 18 cases, interstitial type was seen in 15 cases and diffuse type was observed in 7 cases.

Conclusion: Bone marrow aspiration along with trephine biopsy is essential for the diagnosis and management of multiple myeloma.

A software program, MU-Tomo, has been developed to perform an independent point dose calculation and compare it to the dose calculated from the TomoTherapy (TomoTherapy, Inc., Madison, WI) treatment planning system (TPS). Input parameters required for this software include: archived tomotherapy patient files, QA plan image coordinates, tomotherapy-calculated point dose and machine-specific dosimetric parameters such as the off-axis ratios (OARx and OARy), tissue phantom ratios (TPR) and output functions (Scp). The software was validated on four phantom models and fifty tomotherapy patient plans representing various anatomical sites. Our results indicate that MU-Tomo can perform in a few seconds an independent dose calculation accurately and provide a secondary check for a point dose validation of helical tomotherapy plans.

This work studied on dosimetric impact due to inter-fractional uncertainties for one hundred patients from five different treatment sites (30 prostate, 26 head & neck, 18 lung, 17 pelvis, and 9 brain patients) for Tomotherapy modality. Daily setup shifts were quantified and grouped into systematic (mean daily setup shifts) and random shifts (fractionbased shifts with corresponding systematic shift subtraction). Both systematic and random shifts were incorporated into in-house independent point dose calculation software, MU-Tomo, to separately evaluate the systematic and random dosimetric variations. Systematic dosimetric variations showed large dose deviation, with the largest difference at -10.02% compared to the planned dose and 3% standard deviation. Mean random dosimetric variations showed relatively small dose deviation with the largest at -5.65% compared to the planned dose and 1.9% standard deviation. Furthermore, different treatment sites were sorted into the head & neck and brain group, and the body group including lung, pelvis, and prostate cancers. According to ANOVA analyses, random dosimetric variations were found significantly different between patients treated at the same treatment site, while systematic dosimetric variations were significantly different between the head & neck and brain group and the body group. No significant differences were discovered among specific patients for systematic dosimetric variations, and no significant differences were observed within each of the two groups for random dosimetric variations. Dosimetric consequences are not significantly correlated with treatment fraction number according to the Pearson correlation analysis. By comparing doses without any shift against those with the random shift, overall dosimetric impacts to each patient were found to be very small with the mean value -0.0053% and standard deviation of 1.11%. Ninety-nine percentage of the averaged variation results were within 3.5%. This implies that overall dosimetric impact from random variations is small; instead, dosimetric impact is more affected by systematic shifts.

S-1, an oral anticancer drug, is comprised of tegafur (a prodrug of 5-fluorouracil) and two biochemical modulators that have effect-enhancing and adverse reaction-reducing activities. Neoadjuvant chemotherapy (NAC) using S-1 has not been reported. Between April 2003 and March 2008, 103 patients with previously untreated oral squamous cell carcinoma (OSCC) received some courses of S-1 NAC (S-1 80 mg/m2/day as the NAC until 1 week preoperatively). Tumor size and histopathologic effect were evaluated before and after treatment. Among 103 cases, 10 cases had complete responses and 53 cases had partial responses (overall response rate [RR], 61.2%). Twenty-two (21.4%) patients had adverse events. Most patients had mild toxicities in the bone marrow and digestive tract (grade 1, 19 cases). Only three patients (2.9%) had grade 2 neutropenia or grade 4 thrombocytopenia. We examined the relationship between the RR and the clinicopathologic behaviors. The RR of the pN2 cases (33.3%) was significantly lower than that of the pN0 cases (69.4%). The RR was not correlated with tumor size, differentiation type, distant metastasis, and the period of administration. The data indicates that S-1 caused only mild toxicity and had highly effective antitumor activity. Furthermore, the RR of S-1 NAC might predict regional lymph node metastasis.

Endothelial antigens that stimulate immune-mediated damage of tumor vessels represent possible targets for the development of antiangiogenic vaccines aimed at preventing the progression of solid tumors. Since antigens expressed on the cell surface are accessible targets for both humoral and cell-mediated immune responses, the ability to isolate extracellular protein fragments from endothelial cells by proteolytic digest is a proposed strategy for the creation of antiangiogenic vaccines. Human microvascular endothelial cells (HMEC) were isolated from an abdominal subcutaneous adipose tissue biopsy. Both non-activated endothelial cells (nHMEC) and tumor-activated endothelial cells (aHMEC) were obtained. HMEC lysate and cleaved fragments of cell surface proteins (FCSP) of HMEC had total protein concentrations of 135 µg/mL and 2 µg/mL, respectively. Despite this difference in concentration, FCSP were able to stimulate immune cells in cytotoxicity assays better than the HMEC lysate. Moreover, FCSP obtained from tumor-activated endothelial cells were able to stimulate an immune response toward tumor-activated endothelial cells. Based on these results, FCSP of endothelial cells appear to provide a comprehensive set of surface antigens that are able to induce targeted, immune-mediated cytotoxic effects against tumor endothelial cells. These findings represent a successful strategy to produce safe and pure antigens for the production of antiangiogenic vaccines.