A Prospective Multi-Centered Registry-Based Observational Study for Patients With Cancer: Design and Rationale for Korean Medicine Cancer Registry (KMCARE).

BACKGROUND: Cancer is one of the leading causes of death in most countries with an expected increased burden on healthcare systems. Since integrative medical treatments are not collected within the scope of existing cancer registries, the establishment of the Korean Medicine Cancer Registry (KMCARE), gathering integrative therapies, including conservative care and Korean medicine, is warranted. METHODS: A prospective observational study based on the registry will be conducted in 5 Korean medical hospitals. A total of 650 eligible participants undergoing Korean medicine treatments within 1 month of a diagnosis of lung, colorectal, stomach, or breast cancer are anticipated to be enrolled in the registry. Data collected in the KMCARE can be classified into patient information, received treatments, and outcomes. The primary outcome is the Functional Assessment of Cancer Therapy-General Questionnaire score at 3 months. Secondary outcomes include the MD Anderson Symptom Inventory-Core and the Body Constitution Questionnaire at 3 and 6 months. After 6 months of follow-up periods, survival surveillance will be continued for additional 18 months. Descriptive and statistical analysis of primary and secondary outcomes, baseline data, safety, survival, and prognostic factors will be performed. DISCUSSION: This is the first prospective, multi-centered, registry-based observational study of cancer patients in Korean medicine hospitals, which could reveal the current status of cancer patients receiving integrative cancer therapies, and provide better insight into the role of Korean medicine in palliative care for patients with cancer. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0007447.

Traditional herbal medicine for anorexia in patients with cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of traditional herbal medicine (THM) for improving anorexia in patients with cancer. Methods: We searched for randomized controlled trials (RCTs) that evaluated orally administered THM for cancer-related anorexia using 10 databases from the inception to 1 August 2021. The primary outcome was an improvement in anorexia, measured with the total effective rate (TER) or visual analog scale (VAS). The secondary outcomes were the changes in body weight, the Karnofsky performance scale, acylated ghrelin, and adverse events. We used the Cochrane risk of bias assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation method to assess the quality of the studies and the quality of the evidence. Results: A total of 26 RCTs were included, of which 23 were subjected to quantitative analysis. THM showed a significant improvement in anorexia measured with the TER [risk ratio (RR) 1.12, 95% confidence intervals (CI) 1.04-1.20] than appetite stimulants with moderate quality evidence and in the Karnofsky performance scale (RR 1.38, 95% CI 1.12-1.70) with low quality evidence but not in body weight gain (RR 0.98, 95% CI 0.80-1.20). THM showed a significant improvement in anorexia measured with the TER (RR 1.74, 95% CI 1.23-2.48) compared with usual care with low-quality evidence but did not significantly improve the VAS score (mean difference 0.72, 95% CI 0.00-1.43) or the level of acylated ghrelin (mean difference 0.94, 95% CI 1.08-2.97). There were no serious adverse events. Conclusion: This review suggests that THM may be considered a safe alternative therapeutic option for improving anorexia in patients with cancer. Nonetheless, more rigorous RCTs are needed due to methodological limitations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42021276508.

Impact of traditional East Asian medicine as an add-on therapy on survival and recurrence after surgery for breast cancer: A systematic review and meta-analysis.

Background: Breast cancer is the most common cancer in women. Patients with cancer increasingly incorporate complementary and alternative medicines, including traditional East Asian medicine (TEAM), for cancer prevention and treatment. This review aimed to determine the effectiveness and safety of TEAM for survival and recurrence after surgery in patients with breast cancer. Methods: We searched nine electronic databases up to 25 August 2022, for randomized controlled trials (RCTs) of TEAM to prevent the recurrence of breast cancer in female patients after mastectomy or breast-conserving surgery. The primary outcome was 5-year disease-free survival (DFS), and secondary outcomes were 5-year overall survival, locoregional and distant recurrence rates, and toxicity. This study adhered to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence. Results: From 368 citations, data from nine studies reporting on a total of 1240 patients were included in the systematic review, and eight studies were deemed suitable for the meta-analysis. TEAM combined with adjuvant chemotherapy showed a significant improvement in DFS (odds ratio [OR] 0.42%, 95% confidence interval [CI] 0.28 to 0.61, p < 0.00001) and overall survival (OR 0.44%, 95% CI 0.27 to 0.73, p = 0.001) compared to adjuvant chemotherapy alone. The reduction in the rate of total recurrence was favorable for TEAM combined with adjuvant chemotherapy compared to adjuvant chemotherapy alone (Risk ratio 0.49%, 95% CI 0.35 to 0.70; p < 0.0001). TEAM after adjuvant chemotherapy showed a significant advantage in DFS compared to no TEAM (OR 0.61%, 95% CI 0.41 to 0.92, p = 0.02). No severe adverse events related to TEAM were reported. The overall certainty of the evidence for DFS, overall survival, and the total recurrence rate were moderate when postoperative breast cancer patients used TEAM combined with adjuvant chemotherapy. Conclusion: Moderate-quality evidence suggests TEAM as an add-on therapy to adjuvant chemotherapy. TEAM may have the potential to improve long-term survival and prevent postoperative recurrence in patients with breast cancer. In future, more rigorous RCTs should be conducted to confirm these findings.

Traditional Herbal Medicine for Insomnia in Patients With Cancer: A Systematic Review and Meta-Analysis.

Background: Insomnia is one of the most prevalent cancer-related symptoms and has a severe impact on the quality of life. This study aimed to evaluate the efficacy and safety of traditional herbal medicine (THM) for improving sleep quality in patients with cancer. Methods: Randomized controlled trials (RCTs) evaluating orally administered THM in a cancer population with insomnia were searched using nine electronic databases up to November 30, 2020. The outcome measurements were sleep quality measured by validated questionnaire such as the Pittsburgh Sleep Quality Index (PSQI), total effective rate, and adverse effects. The included studies were appraised using the Cochrane risk of bias tool and meta-analyzed. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Results: Fourteen RCTs were included in the systematic review, and 10 RCTs were analyzed quantitatively. Compared to hypnotics, THM showed a significant improvement in sleep quality by reducing the PSQI score [mean difference (MD) -2.25, 95% confidence interval (CI) -3.46 to -1.05, I 2 = 84%] and increasing the total effective rate [risk ratio (RR) 1.26, 95% CI 1.07 to 1.48, I 2 = 70%] with low quality of evidence. Compared to placebo, THM also reduced the PSQI score significantly (MD -2.56, 95% CI -3.81 to -1.31, I 2 = 91%) with moderate quality of evidence. The most frequently used herbs were Ziziphus jujuba Mill. No serious adverse events were observed. Conclusion: This review suggests that THM may be an effective therapeutic option for insomnia in patients with cancer. However, considering the limited methodological qualities and inconsistent results of the included trials, further rigorous RCTs are required. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], PROSPERO 2021 [CRD42021265070].

Traditional Herbal Medicine, Sipjeondaebo-Tang, for Cancer-Related Fatigue: A Randomized, Placebo-Controlled, Preliminary Study.

PURPOSE: Sipjeondaebo-tang (SDT) is a widely used traditional herbal medicine for relieving fatigue. This randomized, placebo-controlled, preliminary study evaluated SDT for cancer-related fatigue, which is the most common symptom experienced by patients with cancer. PATIENTS AND METHODS: Patients with a Brief Fatigue Inventory (BFI) score of at least 4 were randomly assigned in a double-blinded manner to receive SDT (3 g 3 times daily) or placebo orally for 3 weeks. The BFI was the primary outcome measure and secondary outcome measures included the Hospital Anxiety and Depression Scale (HADS), the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ-C30), immunoregulatory tests, and safety. RESULTS: A total of 50 participants were randomly assigned and 48 patients completed the trial. Based on intention-to-treat analysis, fatigue, which was the primary outcome, was improved in both arms compared with the baseline, and was significantly better in the SDT group than in the placebo group at week 3 (3.56 ± 1.18 vs 4.63 ± 1.83, P = .019). Secondary outcomes, including anxiety, depression, and immunoregulatory tests, did not improve significantly in either group. However, quality of life measured using the EORTC QLQ-C30 improved in both arms compared with the baseline, and the global health subscale was significantly better in the SDT group than in the placebo group (P = .02). No significant toxicities were observed. CONCLUSION: SDT may improve cancer-related fatigue and quality of life in patients with cancer. A further randomized clinical trial with large sample size is warranted.

Traditional herbal medicine combined with first-line platinum-based chemotherapy for advanced non-small-cell lung cancer: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a major health burden in many countries. This review aimed to evaluate the efficacy of traditional herbal medicine (THM) combined with first-line platinum-based chemotherapy (PBCT) for the treatment of advanced NSCLC. METHODS: From inception to April 2021, relevant studies were retrieved from 9 electronic databases. Randomized controlled trials (RCTs) comparing survival outcomes of THM + PBCT treatment with PBCT treatment in patients with advanced NSCLC were reviewed. The risk of bias was evaluated using the Cochrane Risk of Bias Tool. Overall survival, 1-year survival, progression-free survival or time to progression, tumor response rate, and adverse effects were analyzed. RESULTS: Sixteen RCTs comprising 1445 patients were included. The meta-analysis indicated that THM + PBCT treatment, compared to PBCT alone, could improve overall survival (median survival ratio = 1.24, 95% confidence intervals [CI] [1.11, 1.39], P < .001), progression-free survival/time to progression (median survival ratio = 1.22, 95% CI [1.09, 1.37], P < .001), and the 1-year survival rate (risk ratio [RR] = 1.56, 95% CI [1.31, 1.86], P < .001). THM + PBCT also led to a higher tumor response rate (RR = 1.39, 95% CI [1.22, 1.59], P < .001) and lower incidence of thrombocytopenia (RR = 0.72, 95% CI [0.56, 0.92], P = .009) and nausea/vomiting (RR = 0.35, 95% CI [0.21, 0.57], P < .001), while there was no significant effect observed on leukopenia (RR = 0.68, 95% CI [0.34, 1.36], P = .27). CONCLUSION: THM, when used in combination with PBCT, might increase survival and the tumor response rate while decreasing the side effects caused by chemotherapy in patients with advanced NSCLC. However, considering the limited methodological qualities of the included trials, more rigorous RCTs are needed.

Comparative Efficacy of Jaungo, A Traditional Herbal Ointment, and the Water-in-Oil Type Non-Steroidal Moisturizer for Radiation-Induced Dermatitis in Patients With Breast Cancer: A Study Protocol for a Prospective, Randomized, Single-Blinded, Pilot Study.

Background: Radiation-induced dermatitis (RID) is a common complication of radiation therapy (RT). Although it has a high prevalence and can even trigger the premature end of conventional cancer therapies, there is no standard management. This study aims to evaluate whether topical use of Jaungo (Shiunko), a traditional herbal ointment mainly composed of Lithospermi radix and Angelica sinensis, could reduce RID compared to the water-in-oil type non-steroidal moisturizer in patients with breast cancer. Methods: This is a prospective, single-blinded, randomized controlled pilot trial that investigates the effect of topical application of Jaungo for the prevention of RID in postoperative breast cancer patients scheduled for RT, in comparison with the non-steroidal moisturizer, with a random distribution of 50 patients across the two groups. RT will be administered for 5-7 weeks with a biological equivalent dose (BED10) of 60 Gy or more, and the interventions will be applied 3 times a day during RT duration. Participants will be assessed a total of nine times, including eight visits during the period of RT and one visit at a 2-week follow-up period after the end of treatment. The incidence and severity of RID, quality of life, skin reaction symptoms, and maximum pain related to RID will be measured. The incidence rate of grade 2 or higher RID using the Radiation Therapy Oncology Group (RTOG) in the two groups will be statistically compared as the primary outcome. The types and frequencies of adverse events will be also collected and evaluated. All assessments will be performed by independent radiology oncologists. Discussion: This trial is currently ongoing and is recruiting. This study will determine the preventive efficacy of Jaungo in RID with postoperative breast cancer patients and provide evidence in traditional Korean medicine clinical practice.

Efficacy of Chemotherapy Integrated With Traditional Korean Medicine in Patients With Metastatic Pancreatic Cancer: A Single-Center Retrospective Study.

BACKGROUND: This retrospective study investigated the efficacy and safety of chemotherapy (CTX) integrated with Traditional Korean Medicine (TKM) in patients with metastatic pancreatic cancer, in a single Korean center. METHODS: From January, 2014 to February, 2019, patients with metastatic pancreatic cancer who had received CTX were enrolled. Overall survival (OS), demographic characteristics, and adverse events were examined. Statistical analysis was utilized to evaluate the differences in characteristics and to compare the survival rates between the CTX group and CTX+TKM group. Kaplan-Meier curves were used to compare the differences in survival time. A Cox regression analysis was performed to determine the hazard ratio of the risk of mortality. RESULTS: A total 37 participants were included and visited a TKM hospital 7.4 ± 8.3 months after being diagnosed with metastatic pancreatic cancer. The median age of the participants was 62 years; 26 patients (70.3%) had an Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2, and 23 patients (62.2 %) had first-line CTX failure. The median OS of all patients was 3.8 months (95% CI, 3.1-4.6). The CTX + TKM group showed longer survival (4.1 months; 95% CI, 2.4- .8) than the CTX group (2.4 months, 95% CI 0.2-4.6) but this was not statistically significant (P = .217). Chemotherapy with TKM treatment for more than 30 days (CTX + TKM ≥ 30) significantly prolonged median OS (9.1 months; 95% CI, 3.6-14.5; P = .025) compared to chemotherapy alone. Cox hazard ratio analysis revealed that CTX + TKM ≥ 30 and prior chemotherapy were significantly independent prognostic factors for OS. The main herbs in the TKM treatment were Rhus verniciflua Stokes and Astragalus. Severe adverse events with respect to TKM treatment were not reported. CONCLUSIONS: TKM treatment integrated with chemotherapy may prolong OS in patients with metastatic pancreatic cancer compared to chemotherapy treatment alone. More rigorous prospective clinical trials are needed to confirm this result.

Gold Nanoparticles for Photothermal Cancer Therapy.

Gold is a multifunctional material that has been utilized in medicinal applications for centuries because it has been recognized for its bacteriostatic, anticorrosive, and antioxidative properties. Modern medicine makes routine, conventional use of gold and has even developed more advanced applications by taking advantage of its ability to be manufactured at the nanoscale and functionalized because of the presence of thiol and amine groups, allowing for the conjugation of various functional groups such as targeted antibodies or drug products. It has been shown that colloidal gold exhibits localized plasmon surface resonance (LPSR), meaning that gold nanoparticles can absorb light at specific wavelengths, resulting in photoacoustic and photothermal properties, making them potentially useful for hyperthermic cancer treatments and medical imaging applications. Modifying gold nanoparticle shape and size can change their LPSR photochemical activities, thereby also altering their photothermal and photoacoustic properties, allowing for the utilization of different wavelengths of light, such as light in the near-infrared spectrum. By manufacturing gold in a nanoscale format, it is possible to passively distribute the material through the body, where it can localize in tumors (which are characterized by leaky blood vessels) and be safely excreted through the urinary system. In this paper, we give a quick review of the structure, applications, recent advancements, and potential future directions for the utilization of gold nanoparticles in cancer therapeutics.

Optimal Processing Conditions of Boswellia carteri Birdw. Using Response Surface Methodology.

BACKGROUND: Boswellia carteri Bridw. is being widely used for its anti-inflammatory properties, as well as for wound healing, antimicrobial, and immunomodulatory properties, and boswellic acids (BAs) are considered to be the main active constituents. OBJECTIVES: To investigate optimal conditions of stir-baking process for the resin of B. carteri with vinegar of using response surface methodology (RSM). MATERIALS AND METHODS: The concentration of acetic acid, heating temperature, and heating time were set as influential factors, and the yields of chemical compounds were the response values which were optimally designed by a Box-Behnken design. The amounts of 11-keto-ß-boswellic acid (KBA) and α-boswellic acid (αBA) in B. carteri resin were quantified using high-performance liquid chromatography analysis. RESULTS: Maximum amounts of KBA and αBA in B. carteri resin were obtained using 6% acetic acid for 10 min at 90°C in preliminary test. Two factor interactions, such as acetic acid concentration-heating temperature and heating temperature-heating time, were significantly observed by multiple regression analysis. Optimal processing conditions from RSM were 5.83% for acetic acid concentration, 9.56 min for heating time, and 89.87°C for heating temperature. Under the modified conditions, the experimental value of the response was 11.25 mg/g, which was similar to the predicted value. CONCLUSIONS: The results suggest that the optimal conditions for the stir-baking process of B. carteri resin were determined by RSM, which was reliable and applicable to practical processing of herbal medicine. SUMMARY: The resin of Boswellia carteri was macerated in aqueous acetic acid and heated using an oven for stir baking processThe interaction between heating temperature and heating time was the most significantOptimal conditions for processing B. carteri resin were determined as 5.83% acetic acid, 9.56 min for heating time, and 89.87°C for heating temperature. Abbreviations used: BAs: Boswellic acids; KBA: 11 keto ß boswellic acid; αBA: α boswellic acid; BBD: Box-Behnken design; RSM: Response surface method; HPLC: High performance liquid chromatography; LOD: Limits of determination; LOQ: Limits of quantification; RSD: Relative standard deviation; ANOVA: Analysis of variance.

A Drosophila Reporter for the Translational Activation of ATF4 Marks Stressed Cells during Development.

Eukaryotic cells have evolved signaling pathways that help to restore cellular homeostasis in response to various physiological or pathological conditions. ATF4 is a transcription factor whose mRNA translation is stimulated in response to stress-activated eIF2alpha kinases. Established conditions that activate eIF2alpha phosphorylation and ATF4 translation include excessive stress in the endoplasmic reticulum (ER) and amino acid deprivation. ATF4 is activated through a unique translational activation mechanism that involves multiple upstream open reading frames (uORFs) in the 5'-untranslated region (UTR), which is conserved from yeast to mammals. Taking advantage of this, we developed a translational activation reporter of ATF4 in Drosophila, in which the dsRed reporter coding sequence was placed downstream of the Drosophila ATF4 5' UTR. This reporter remained inactive in most tissues under normal conditions, but showed dsRed expression when starved, or when challenged with conditions that imposed ER stress. In normally developing flies, a small number of cell types showed reporter expression even without exogenous stress, which included the salivary gland, gut, the male reproductive organ, and the photoreceptor cells, suggestive of inherent stress during the normal development of these cell types. These results establish a new tool to study ATF4-mediated stress response in Drosophila development and disease.

Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis isolates from Korea and analysis of the correlation between the mutations and pyrazinamidase activity.

To investigate the effect of natural pyrazinamidase (PncA) mutations on protein function, we analyzed expression and PncA activity of eight pncA point mutants identified in nineteen pyrazinamide-resistant Mycobacterium tuberculosis clinical isolates. Among them, two mutants (Y99D and T135P) showed high expression level and solubility comparable to those of the wild-type PncA protein, two (K48E and G97D) displayed low expression level and solubility, and four (C14R, H51P, W68S, and A146V) were insoluble. Interestingly, when possible structural effects of these mutations were predicted by the CUPSAT program based on the proposed three-dimensional structure of M. tuberculosis PncA, only two highly soluble mutant proteins (Y99D and T135P) were predicted to be stabilizing and have favorable torsion angles. However, the others exhibiting either low solubility or precipitation were foreseen to be destabilizing and/or have unfavorable torsion angles, suggesting that the alterations could interfere with proper protein folding, thereby decreasing or depleting protein solubility. A PncA activity assay demonstrated that two mutants (G97D and T135P) showed virtually no activity, but two other mutants (K48E and Y99D) exhibited wild-type activity, indicating that the PncA residues (Cys14, His51, Trp68, Gly97, Thr135, and Ala146) may be important for PncA activity and/or proper protein folding.

HIV-1 Tat interacts with and regulates the localization and processing of amyloid precursor protein.

HIV-1 Tat protein plays various roles in virus proliferation and in the regulation of numerous host cell functions. Accumulating evidence suggests that HIV-1 Tat also plays an important role in HIV-associated neurocognitive disorders (HAND) by disrupting intracellular communication. Amyloid beta (Aß) is generated from amyloid precursor protein (APP) and accumulates in the senile plaques of Alzheimer's disease patients. This study demonstrates that Tat interacts with APP both in vitro and in vivo, and increases the level of Aß42 by recruiting APP into lipid rafts. Co-localization of Tat with APP in the cytosol was observed in U-87 MG cells that expressed high levels of Tat, and redistribution of APP into lipid rafts, a site of increased ß- and γ-secretase activity, was demonstrated by discontinuous sucrose density gradient ultracentrifugation in the presence of Tat. Furthermore, Tat enhanced the cleavage of APP by ß-secretase in vitro, resulting in 5.5-fold higher levels of Aß42. This was consistent with increased levels of ß-C-terminal fragment (ß-CTF) and reduced levels of α-CTF. Moreover, stereotaxic injection of a lentiviral Tat expression construct into the hippocampus of APP/presenilin-1 (PS1) transgenic mice resulted in increased Tat-mediated production and processing of Aß in vivo. Increased levels of Aß42, as well as an increase in the number and size of Aß plaques, were observed in the hippocampus following injection of Tat virus compared with mock virus. These results suggest that HIV-1 Tat may contribute to HAND by interacting with and modifying APP processing, thereby increasing Aß production.

Simple and rapid discrimination of embB codon 306 mutations in Mycobacterium tuberculosis clinical isolates by a real-time PCR assay using an LNA-TaqMan probe.

Single nucleotide polymorphisms in the codon 306 of embB gene are most frequently reported in ethambutol-resistant Mycobacterium tuberculosis clinical isolates. Here, we report a simple and rapid real-time PCR assay using a locked nucleic acid (LNA)-TaqMan probe for discriminating the embB306 mutations. The use of a 15-bp chimeric LNA/DNA probe led to a relatively higher level of sensitivity and fluorescence signal in the wild-type embB306 ATG codon. Therefore, the mutant alleles were easily distinguishable from the wild-type allele by their distinctive amplification curve shapes without a melting analysis of the PCR product. This system was fast and less than 0.1 pg of genomic DNA per reaction was needed for detection. Because the results from this real-time assay were absolutely consistent with those from DNA sequencing, it can be effectively applied as a simple and rapid method for primary screening of embB306 mutations that occur frequently in ethambutol-resistant and/or multidrug-resistant M. tuberculosis isolates.

Molecular characterization of drug-resistant and -susceptible Mycobacterium tuberculosis isolated from patients with tuberculosis in Korea.

We investigated the causal relationship between genotype and phenotype of drug-resistant Mycobacterium tuberculosis isolates obtained from patients with pulmonary tuberculosis (TB) in Korea. Of 80 isolates tested, 17, 20, 1, and 7 isolates were mono-resistant to ethambutol (EMB), isoniazid (INH), pyrazinamide (PZA), and rifampicin (RFP), respectively, and 31 isolates (38.8%) were multidrug-resistant (MDR). Sequencing analysis showed that 78% (32/41) of RFP-resistant strains had mutations in the rifampicin resistance-determining region (RRDR) of rpoB, and the mutation at rpoB531 (59.4%) was most abundant. In 52 INH-resistant strains, mutations were found mostly at C-15T (n = 21, 40.4%) in the inhA promoter region as well as at katG315 (n = 12, 23.1%). Mutations at embB306 were mostly found in 26.7% (12/45) of EMB-resistant isolates. New mutations found here in MDR isolates include rpoB523 (Gly523Glu) and embB319 (Tyr319Ser). Consequently, mutations in the rpoB531, C-15T in the inhA promoter region, embB306, and katG315 would be a useful marker for rapid detection of MDR M. tuberculosis isolates in Korea.

Molecular cloning, purification, and characterization of a superoxide dismutase from a fast-growing Mycobacterium sp. Strain JC1 DSM 3803.

A cytosolic superoxide dismutase (SOD) was purified and characterized from a fast-growing Mycobacterium sp. strain JC1 DSM 3803 grown on methanol. The native molecular weight of the purified SOD was estimated to be 48 kDa. SDS-PAGE revealed a subunit of 23 kDa, indicating that the enzyme is a homodimer. The enzyme activity was inhibited by H(2)O(2) and azide. The purified SOD contained 1.12 and 0.56 g-atom of Mn and Fe per mol of enzyme, respectively, suggesting that it may be a Fe/Mn cambialistic SOD. The apo-SOD reconstitution study revealed that Mn salts were more specific than Fe salts in the SOD activity. The gene encoding the SOD was identified from the JC1 cosmid genomic library by PCR screening protocol. The cloned gene, sodA, had an open reading frame (ORF) of 624 nt, encoding a protein with a calculated molecular weight of 22,930 Da and pi of 5.33. The deduced SodA sequence exhibited 97.6% identity with that of Mycobacterium fortuitum Mn-SOD and clustered with other mycobacterial Mn-SODs. A webtool analysis on the basis of SOD sequence and structure homologies predicted the SOD as a tetrameric Mn-SOD, suggesting that the protein is a dimeric Mn-SOD having tetramer-specific sequence and structure characteristics.