The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed ‘CKDB-315’. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George’s Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.
Although dendritic cells (DC) have been well demonstrated as a strong cellular adjuvant for a tumor vaccine, there are several limitations for clinical application. A protein‐based vaccine using a potent adjuvant is an appealing approach for tumor antigen‐specific immunotherapy because of their simplicity, safety, efficacy and capacity for repeated administration. CpG‐oligodeoxynucleotides (ODN) have been used as adjuvants to stimulate innate and adaptive immune responses for cancer treatment. The authors evaluated the adjuvant effects of CpG‐ODN in a vaccine incorporating recombinant fusion protein of the HIV TAT PTD domain and carcinoembryonic antigen (TAT‐CEA). Mice vaccinated with TAT‐CEA and CpG‐ODN (TAT‐CEA + CpG) showed enhanced CEA‐specific immunity, including cytotoxic T‐lymphocytes (CTL) activity and interferon (IFN)‐γ secreting T cells compared with CEA and CpG‐ODN (CEA + CpG) or TAT‐CEA vaccination alone. Vaccination with TAT‐CEA + CpG elicited Th1‐based responses, as indicated by the higher ratio of immunoglobulin (Ig)G2a antibody/IgG1 antibodies specific for CEA. The survival rate was significantly increased after vaccination with TAT‐CEA + CpG in a tumor model using MC38/CEA2. Furthermore, the TAT‐CEA ± CpG vaccine groups showed similar antitumor immunity to the CEA peptide‐pulsed DC (CEA peptide/DC) vaccine groups. These data suggest that coadministration of TAT fusion protein with CpG‐ODN may serve as a potential formulation for enhancing antitumor activity. ( Cancer Sci 2008; 99: 1034–1039)
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Local recurrence rates have markedly decreased in recent years as a result of changes in the surgical approach, such as a total mesorectal excision, as well as, neoadjuvant therapy for, the treatment of patients with colorectal cancer. For the treatment of patients with recurrent rectal cancer, a curative surgical resection of the local recurrence is considered the most important factor affecting the prognosis. However, such a resection is highly challenging as the surgical field has generally been anatomically disrupted and irradiated, and the tumor is typically adherent to or invasive into organs in the middle and low pelvis. And, such a resection is not always possible for all patients with recurrent rectal cancer, so the proper selection of patients for the surgery is very important [1,2]. If an R0 resection is impossible, chemotherapy or radiotherapy may be offered.
In terms of optimizing radiotherapy, the tumors should receive a high total dose while sparing the surrounding normal tissue to avoid toxicity. Dose escalation has also been suggested as possibly being of benefit in the treatment of patients with rectal cancer [3]. Development of new radiotherapy techniques, such as three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and image-guided radiation therapy, has made feasible the delivery of higher doses of external beam radiation with acceptable morbidity. However, if the patient has previously undergone radiotherapy either before or after the primary rectal cancer surgery, determining the proper dose of radiation is challenging because the surrounding normal tissues may have already received doses near the organ- or endpoint-specific tolerance dose during the primary treatment [4]. Because re-irradiation for the treatment of patients with recurrent rectal cancer is mostly given with hyperfractionated (twice daily) chemoradiotherapy to a total dose of 30–40 Gy [4], dose-escalated radiotherapy usually can be performed only for those patients who have not previously undergone radiotherapy.
The authors reviewed the records of patients who had been treated with palliative radiotherapy for locally recurrent colorectal cancers [5]. They reported that salvage radiotherapy, especially dose-escalated radiotherapy, for the treatment of such patients might be beneficial in that it might reduce the risk of progression. However, complete responses are rarely achieved even with high doses radiotherapy, and as expected, in this study, with one exception, dose-escalated radiotherapy was only offered to patients with no history of previous radiotherapy. In a clinical setting, the distinction between curative and palliative intent is often not clear and may depend on whether the patient is eligible for a curative resection after radiotherapy. Therefore, patients with recurrent rectal cancer should undergo adequate re-evaluation and have repeated discussions with a multidisciplinary team on topics such as dose-escalated radiotherapy, chemotherapy and surgical resection.
We intended to identify the oncological outcome for rectal cancer over the past 20 years and whether or not sphincter-preserving surgery is an appropriate approach for low-lying rectal cancer.The oncological outcomes from a total of 418 patients who electively underwent rectal cancer surgery for a lesion located within 8 cm of the anal verge by a single colorectal surgeon were reviewed retrospectively.Of 418 patients, 175 patients underwent low anterior resection (LAR), 172 laparoscopic abdominal transanal proctocolectomy with coloanal anastomosis (LATA), and 71 abdominoperineal resection (APR). The factors related to the disease-free survival (DFS) were neoadjuvant chemoradiation (P = .016), pathologic stage (P < .001), circumferential margin involvement (P < .001), and initial (P = .016) and postoperative serum carcinoembryonic antigen level (P < .001). The factors related to the overall survival (OS) were similar with those related to DFS. Compared with DFS, OS, and local recurrence among three surgical techniques, APR was significantly poorer in DFS (P < .001), OS (P < .001), and local recurrence (P = .001), than was LAR or LATA.The LATA procedure is a technically feasible and oncologically safe surgical option for low-lying rectal cancer. We suggest that LATA may be a good surgical option in selective low-lying rectal cancer patients.
RNA electroporation as a gene delivery method is more feasible and safer as compared with viral vectors. RNA-loaded dendritic cells (DC) have been used to induce T cell responses against tumor rejection antigens and B cells can also act as antigen-presenting cells for cellular vaccines. In this study, we compared B cells and DC, after electroporation with carcinoembryonic antigen (CEA) RNA, for their capacity to generate cytotoxic T lymphocytes and antitumor immunity. Vaccination using these B cells induced levels of IFN-gamma-secreting T cells and cytotoxic T cells comparable to those induced by DC. Intravenous administration was the optimum route for the B cell vaccine, while subcutaneous administration was the optimum route for the DC vaccine. The B cell vaccine predominantly generated CEA-specific CD4(+) T cells, whereas the DC vaccine generated CD8(+) T cells. Moreover, the B cell vaccine induced higher levels of anti-CEA antibodies than the DC vaccine. A heterogeneous prime-boost using B cells and DC failed to show any synergistic effects; however, the B cell vaccine did inhibit tumor growth and prolonged survival to a similar extent as the DC vaccine. Such RNA-electroporated B cells may prove useful as cellular tumor vaccines with potential clinical application.
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