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Colon tumors with deficient DNA mismatch repair (dMMR) are generally infiltrated by T cells more densely than tumors with proficient mismatch repair (pMMR). However, high numbers of tumor-infiltrating lymphocytes (TILs) are found in select pMMR tumors, and low numbers of TILs are seen in select dMMR tumors. In this study, we compared T-cell repertoires in 20 pMMR and 27 dMMR colon tumors with high and low TIL counts. We found that T cells in dMMR tumors are more clonal and their repertoire is less rich compared with T cells in pMMR tumors. In the dMMR group, T cells in TIL-high tumors were more clonal and their repertoire was less rich compared with T cells in TIL-low tumors, but in the pMMR group, T-cell diversity in TIL-high tumors was comparable to T-cell diversity in TIL-low tumors. These findings suggest that T cells clonally expand in dMMR tumors, possibly in response to MMR deficiency-induced tumor neoantigens.

To assess the effect of an insole with subtalar strapping on patients with medial compartment osteoarthritis (OA) of the knee.Novel lateral wedged insoles with elastic subtalar strapping (the subtalar strapping support group) and ankle supporters with a lateral wedged heel insert (the sock-type ankle support group) were prepared. Eighty-eight female outpatients with knee OA were treated with 1 of the 2 insoles for 8 weeks. Femorotibial angle was assessed by standing radiographs with and without unilateral insole use for each subject. Symptoms of knee OA were evaluated according to the severity index of Lequesne et al at baseline and at the final assessment.Participants wearing the insole with subtalar strapping (n = 42) demonstrated significantly decreased femorotibial angle (an average of change: -3.1 degrees +/- 2.5 degrees, P0.0001), but a significant difference was not found in the sock-type ankle support group (n = 46; -0.4 degrees +/- 1.1 degrees, P0.05). In the subtalar strapping support group, pain during bed rest with full extension of the knee (P0.0001), pain after getting up (P = 0.04), pain on getting up from a seated position (P = 0.021), maximum distance walked (P = 0.009), and aggregate severity score (P0.0001) were significantly improved compared with baseline. In contrast, significant symptomatic improvement was detected only in the aggregate score (P = 0.016) in the sock-type ankle support group, but not in any of the 10 specific categories.The lateral wedged insole with subtalar strapping induces correction of the femorotibial angle and symptomatic relief in patients with varus-deformity knee OA.

Canine malignant melanoma (CMM) is a spontaneous, aggressive, and metastatic neoplasm. Preclinical mouse studies have shown that xenogeneic DNA vaccination with genes encoding tyrosinase family members can induce antibody and cytotoxic T-cell responses, resulting in tumor rejection. These studies provided the rationale for a trial of xenogeneic DNA vaccination in CMM using the human tyrosinase gene.Three cohorts of three dogs each with advanced (WHO stage II, III, or IV) CMM received four biweekly i.m. injections (dose levels 100, 500, or 1500 micro g, respectively/vaccination) of human tyrosinase plasmid DNA i.m. via the Biojector2000 delivery device.Mild local reactions at injection sites were the only toxicities observed, with no signs of autoimmunity. One dog with stage IV disease had a complete clinical response in multiple lung metastases for 329 days. Two dogs with stage IV disease had long-term survivals (421 and 588+ days) in the face of significant bulky metastatic disease, and two other dogs with locally controlled stage II/III disease had long-term survivals (501 and 496 days) with no evidence of melanoma on necropsy. Four other dogs were euthanized because of progression of the primary tumor. The Kaplan-Meier median survival time for all nine dogs was 389 days.The results of this trial demonstrate that xenogeneic DNA vaccination of dogs with advanced malignant melanoma is a safe and potentially therapeutic modality. On the basis of these results, additional evaluation of this novel therapeutic is warranted in locally controlled CMM and advanced human melanoma.

To investigate anthropometric measures that closely correlate with symptomatic relief of osteoarthritis (OA) of the knee in response to lateral wedged insole use.Seventy-one patients with medial compartment knee OA were treated with insoles with subtalar strapping or insoles with talonavicular strapping. Randomization was performed according to birth date. The following variables were evaluated: age, disease duration, Kellgren-Lawrence radiographic stage, body mass index, percent body fat, waist to hip ratio, lower extremity lean body mass (L-LBM) per body weight, and radiographic femorotibial angle at baseline. The trial lasted 8 weeks. The correlation between each variable and the remission score (delta score) using the Lequesne index of severity was analyzed.In the subtalar strapping group (n = 34), delta score of knee OA was more strongly associated with age (p = 0.004, r = 0.48) than other variables. A significant correlation was also observed between L-LBM per body weight and delta score (p = 0.041, r = -0.36) in the subtalar strapping group. No other variables significantly correlated with the delta score in the subtalar strapping groups. No variable significantly correlated with the ? score in the talonavicular strapping group (n = 37).We previously reported that use of insoles with subtalar strapping leads to valgus realignment of the femorotibial angle in patients with knee OA with varus deformity, and it may have a similar therapeutic effect to that of high tibial osteotomy. These data suggest that the insole with subtalar strapping is more efficacious for younger patients and those with a higher L-LBM per body weight, and less efficacious for older patients with sarcopenia.