The effects of pterygomaxillary disjunction in surgically assisted rapid maxillary expansion: A systematic review and meta-analysis.

OBJECTIVE: This study aims to assess the expansive effects of pterygomaxillary disjunction (PMD) in surgically assisted rapid maxillary expansion (SARME) surgery using a meta-analysis approach. MATERIALS AND METHODS: The study conducted a comprehensive literature search across five databases: PubMed, Scopus, Medline, Embase, and Cochrane, adhering to the PRISMA 2020 guidelines. Dental alterations were assessed using either cone-beam computed tomography (CBCT) or dental casts, while skeletal changes were exclusively measured from CBCT scans. We analysed the dentoskeletal changes between PMD +/- groups and conducted a within-group comparison. The primary focus of the results was on the mean differences observed in pre- and post-operative measurements. RESULTS: Dental expansion was larger in the PMD+ group but not statistically significant. Skeletal expansion showed a significantly larger expansion in the posterior region in the PMD+ group (P = .033). Without PMD, anterior palatal expansion was significantly larger (P = .03), and the buccal tipping of posterior teeth was also significantly larger (P = .011) to achieve acceptable dental expansion outcomes. CONCLUSIONS: Both PMD +/- groups of SARME surgery can achieve satisfactory dental expansion outcomes. However, bone expansion and tooth inclination are also important factors that influence orthodontic treatment and post-expansion stability. By reducing the bony resistance with PMD, larger posterior palatal expansion and more parallel bony expansion are observed. In contrast, without PMD, there is smaller palatal expansion and greater tooth inclination in the posterior region. This could potentially lead to compromised periodontal conditions following expansion.

Allyl Isothiocyanate Suppresses the Proliferation in Oral Squamous Cell Carcinoma via Mediating the KDM8/CCNA1 Axis.

The dysregulated expression of cyclin genes can lead to the uncontrolled proliferation of cancer cells. Histone demethylase Jumonji-C domain-containing protein 5 (KDM8, JMJD5) and cyclin A1 (CCNA1) are pivotal in cell cycle progression. A promising candidate for augmenting cancer treatment is Allyl isothiocyanate (AITC), a natural dietary chemotherapeutic and epigenetic modulator. This study aimed to investigate AITC's impact on the KDM8/CCNA1 axis to elucidate its role in oral squamous cell carcinoma (OSCC) tumorigenesis. The expression of KDM8 and CCNA1 was assessed using a tissue microarray (TMA) immunohistochemistry (IHC) assay. In vitro experiments with OSCC cell lines and in vivo experiments with patient-derived tumor xenograft (PDTX) and SAS subcutaneous xenograft tumor models were conducted to explore AITC's effects on their expression and cell proliferation. The results showed elevated KDM8 and CCNA1 levels in the OSCC patient samples. AITC exhibited inhibitory effects on OSCC tumor growth in vitro and in vivo. Additionally, AITC downregulated KDM8 and CCNA1 expression while inducing histone H3K36me2 expression in oral cancer cells. These findings underscore AITC's remarkable anticancer properties against oral cancer, highlighting its potential as a therapeutic option for oral cancer treatment by disrupting the cell cycle by targeting the KDM8/CCNA1 axis.

Comparison of the accuracy of diagnoses of oral potentially malignant disorders with dysplasia by a general dental clinician and a specialist using the Taiwanese Nationwide Oral Mucosal Screening Program.

Screening for oral potentially malignant disorders (OPMDs) with dysplasia in high-risk groups is suggested in countries with a high prevalence of the disorders. This study aimed to compare the accuracy of diagnoses of OPMDs with dysplasia made by a primary examiner (general dental clinician) and a specialist (oral and maxillofacial surgeon) using the current Taiwanese Nationwide Oral Mucosal Screening Program (TNOMSP). A total of 134 high-risk participants were enrolled for oral mucosal screening via the TNOMSP. A primary examiner and a specialist examined each participant. Mucosal biopsies were obtained and subjected to histopathological analysis. The OPMD most frequently diagnosed by the primary examiner was thin homogeneous leukoplakia (48/134; 35.8%), and in 39/134 participants (29.1%) the diagnosis was uncertain, but abnormalities were suggested. The OPMDs most frequently diagnosed by the specialist were erythroleukoplakia (23/134; 17.2%) and thin homogeneous leukoplakia (21/134; 15.7%), and 51/134 participants (38.1%) were diagnosed with other diseases. Via histopathology, 70/134 participants (52.3%) were diagnosed with dysplasia, and 58/134 (43.3%) were diagnosed with benign conditions. The specialist's diagnoses exhibited a higher specificity, positive predictive value, and accuracy than the primary examiners. A specialist using the current TNOMSP for high-risk participants diagnosed OPMDs with dysplasia more accurately than a primary examiner. Early diagnosis of high-risk OPMDs is crucial in countries with a high prevalence of the disorders. Proficient examination via the current TNOMSP by trained clinician is effective for the management of OPMDs with dysplasia.

Triptolide suppresses oral cancer cell PD-L1 expression in the interferon-γ-modulated microenvironment in vitro, in vivo, and in clinical patients.

Biological and prognostic roles of programmed death ligand 1 (PD-L1) remain unclear in oral squamous cell carcinoma (OSCC). Moreover, the pivotal role of tumor microenvironmental interferon-gamma (IFN-γ) in host responses to malignant cells, oral cancer growth, and PD-L1 expression has not been adequately studied. Thus, PD-L1 expression in 130 OSCC samples was analyzed using immunohistochemistry, which was found significantly overexpressed at the tumor site (P < .01). We further analyzed the effects of IFN-γ on OSCC cell proliferation using enzyme-linked immunosorbent assays and found that IFN-γ drives PD-L1 expression in OSCC cells in a dose-dependent manner. Triptolide (TPL), a bioactive compound isolated from Tripterygium wilfordii, exhibits anti-inflammatory and antitumor activities. To investigate whether the antitumor effect of TPL involves the suppression of PD-L1 expression, we treated OSCC cells in vitro and a patient-derived tumor xenograft (PDTX) model with TPL. TPL suppressed PD-L1 expression in the PDTX model, inhibiting tumor growth, and in OSCC cells in an IFN-γ-modulated microenvironment. We concluded that TPL inhibits tumor growth in oral cancer and downregulates PD-L1 expression in oral cancer cells in vitro. Our results provide evidence for the clinical development of PD-L1-targeted therapy for OSCC.

Downregulation of Jumonji-C domain-containing protein 5 inhibits proliferation by silibinin in the oral cancer PDTX model.

Dysregulation of histone demethylase Jumonji-C domain-containing protein 5 (JMJD5) has been identified as a great effect on tumorigenesis. Silibinin is a commonly used anti-hepatotoxic drug and exhibits anticancer effect in various cancers. However, the antitumor mechanism between silibinin and JMJD5 in oral squamous cell carcinoma (OSCC) remains unclear. In this study, the clinical significance of JMJD5 on OSCC patients was assessed through tissue microarray. Furthermore, mice bearing patient-derived tumor xenografts (PDTXs) and tongue cancer cell lines were treated with silibinin and evaluated for tumor growth and JMJD5 expression. High expression of JMJD5 in oral cancer was significantly associated with tumor size (P = 0.0241), cervical node metastasis (P = 0.0001) and clinical stage (P = 0.0002), was associated with worse survival rate compared with that of the total cohort (P = 0.0002). Collectively the data indicate that JMJD5 expression may be suitable for detection of unfavorable prognosis in OSCC patients, based in part on its apparent role as a marker of metastasis. In addition, silibinin inhibits cancer growth in vitro and in PDTX models. Furthermore, metastasis-associated protein 1 (MTA1) could regulate the expression for JMJD5 and had a positive correlation with JMJD5. Moreover, silibinin could downregulate JMJD5 and MTA1 in oral cancer. Present study thus identifies that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression. In addition, silibinin is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating JMJD5 in OSCC, through a mechanism likely involving MTA1/JMJD5 axis.

Molecular heterogeneity unravelled by single-cell transcriptomics in patients with essential thrombocythaemia.

Significant phenotypic heterogeneity exists in patients with all subtypes of myeloproliferative neoplasms (MPN), including essential thrombocythaemia (ET). Single-cell RNA sequencing (scRNA-Seq) holds the promise of unravelling the biology of MPN at an unprecedented level of resolution. Herein we employed this approach to dissect the transcriptomes in the CD34+ cells from the peripheral blood of seven previously untreated ET patients and one healthy adult. The mutational profiles in these patients were as follows: JAK2 V617F in two, CALR in three (one type I and two type II) and triple-negative (TN) in two. Our results reveal substantial heterogeneity within this enrolled cohort of patients. Activation of JAK/STAT signalling was recognized in discrepant progenitor lineages among different samples. Significantly disparate molecular profiling was identified in the comparison between ET patients and the control, between patients with different driver mutations (JAK2 V617F and CALR exon 9 indel), and even between patients harbouring the same driver. Intra-individual clonal diversity was also found in the CD34+ progenitor population of a patient, possibly indicating the presence of multiple clones in this case. Estimation of subpopulation size based on cellular immunophenotyping suggested differentiation bias in all analysed samples. Furthermore, combining the transcriptomic information with data from targeted sequencing enabled us to unravel key somatic mutations that are molecularly relevant. To conclude, we demonstrated that scRNA-Seq extended our knowledge of clonal diversity and inter-individual heterogeneity in patients with ET. The obtained information could potentially leapfrog our efforts in the elucidation of the pathogenesis of the disease.

Pretreatment body mass index as a prognostic predictor in patients with oral squamous cell carcinoma.

OBJECTIVES: To evaluate whether low body mass index (BMI) is a potential adverse prognostic factor in patients with oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: This cross-sectional study included 320 patients with OSCC who underwent therapeutic surgical treatment in Taiwan. The pretreatment BMI was measured as a common indicator of the pretreatment nutritional status to calculate the overall survival in Kaplan-Meier method. The adverse histopathological features of margin status, depth of invasion (DOI), lymphovascular invasion (LVSI), perineural invasion (PNI), and extranodal extension (ENE) were analyzed using the Cox regression model. RESULTS: Low BMI (underweight), DOI > 5 mm, and ENE were identified as detrimental prognostic factors. On multivariate Cox regression analysis, the low BMI group (odds ratio [OR] = 1.683; 95% confidence interval [95% CI] 1.116-2.539; P = 0.022), DOI > 5 mm (OR = 2.399; 95% CI 1.459-3.943; P = 0.001), and ENE (OR = 2.467; 95% CI 1.540-3.951; P = 0.000) yielded reduced survival rate. CONCLUSIONS: The lower BMI had an important and significant effect on the survival of patients with oral cancer and their surgical outcomes. In addition to the adverse histopathological features, a DOI > 5 mm and positive ENE were also identified as the most important prognostic factors. CLINICAL RELEVANCE: Underweight patients with low BMI, DOI of > 5 mm, and positive ENE should receive more intensive nutritional supplementation and postoperative adjuvant therapy.

A histopathological evaluation and potential prognostic implications of oral squamous cell carcinoma with adverse features.

OBJECTIVES: This study aimed to evaluate the adverse clinicopathologic features of oral squamous cell carcinoma (OSCC), including margin status, depth of invasion, lymphovascular invasion, perineural invasion, and extranodal extension that significantly affect survival outcomes. MATERIALS AND METHODS: This retrospective cross-sectional study included 341 patients with OSCC who underwent therapeutic surgical treatment in Taiwan. The Kaplan-Meier method was used to estimate survival outcomes. A multivariable Cox regression model was used to evaluate the associations of various clinicopathologic features with 5-year overall survival (OS) outcomes in patients with pN0 and pN+ tumors. RESULTS: Overall, the patients had 5-year OS and progression-free survival rates of 60.0 and 47.9%, respectively. In the pN0 group, the multivariate analysis identified a positive margin (odds ratio [OR] = 16.3, 95% confidence interval [95% CI]: 3.7-72.3; P = 0.001), depth of invasion >5 mm (OR = 2.1, 95% CI: 1.2-3.7; P = 0.012), presence of lymphovascular space invasion (OR = 5.4, 95% CI: 1.3-22.0; P = 0.018), and presence of perineural invasion (OR = 4.3, 95% CI: 1.7-11.1; P = 0.002) as independent and significant prognosticators of OS. In the pN+ group, only the presence of extranodal extension independently predicted OS (OR = 1.7, 95% CI: 1.1-2.7; P = 0.0026). CONCLUSIONS: When determining survival prognosis for patients with a pN0 status, we recommended including all adverse features. In contrast, extranodal extension was the most important prognostic factor for patients with a pN+ status.

Comparison of the hospitalization period after microvascular reconstruction flap in trismus patients: free anterolateral thigh flap versus free forearm flap.

OBJECTIVES: The primary strategy for treating oral squamous cell carcinoma (OSCC) is therapeutic resection, with the trismus resection defect reconstructed via free flap. The most popular free flaps include the radial forearm free flap (RFFF) and anterolateral thigh free flap (ALT). This study investigated the relationships between the hospitalization period and a variety of surgical outcomes, as well as maximum inter-incisor distance (IID), in trismus patients who chewed betel nuts. MATERIALS AND METHODS: Forty-nine primary OSCC patients who chewed betel nuts and underwent surgical resection and reconstruction between 2010 and 2016 were enrolled in this retrospective study. The data were from a single center in Taiwan. The outcome variable after flap recovery surgery was the duration of postoperative hospitalization. Other factors that were analyzed comprised correlations between hospitalization and a variety of factors, including postoperative inter-incisor distances (IIDs), operative time, gender, and WBC count, upon stratification into two reconstruction groups. RESULTS: The mean postoperative hospitalization duration in the ALT group was 22.9 ± 7.2 days, which was significantly shorter than that in the RFFF group (27.8 ± 7.0 days; p = 0.019). Two-week postoperative IID (ALT group: 16.1 ± 0.8 mm; RFFF group: 7.0 ± 0.6 mm) was inversely related to the duration of hospitalization (p = 0.022, r = - 0.372). CONCLUSIONS: The ALT flap is more effective than the RFFF flap to reduce the length of hospitalization in trismus patients. CLINICAL RELEVANCE: The ALT flap should be considered as a first-line technique in OSCC reconstruction in trismus patient reconstruction.

Anti-oral cancer effects of triptolide by downregulation of DcR3 in vitro, in vivo, and in preclinical patient-derived tumor xenograft model.

BACKGROUND: Aberrant expression of decoy receptor 3 (DcR3) is considered to be a diagnostic and therapeutic target for human cancers. The aim of this study was to assess DcR3 as a target of the anticancer effects of triptolide (TPL) in preclinical patient-derived tumor xenograft (PDTX) models of oral squamous cell carcinoma (OSCC). METHODS: The expression of DcR3 was evaluated through immunohistochemistry, and correlations were examined using clinical variables. The effects of TPL on the expression of DcR3 and cell proliferation were investigated in OSCC cell lines and in PDTX models. RESULTS: DcR3 overexpression was associated with overall survival and tumor size. TPL significantly decreased tumor growth. Moreover, TPL inhibited the expression of metastasis-associated protein 1 (MTA1), a transcription factor for DcR3 in vivo, in vitro, and in PDTX models. CONCLUSION: TPL appeared to exert anticancer effects by repressing DcR3 and MTA1 in vitro, in vivo, and in PDTX models.

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

OBJECTIVES: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. MATERIAL AND METHODS: We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. RESULTS: Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). CONCLUSIONS: Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. CLINICAL RELEVANCE: LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

Danshen extract circumvents drug resistance and represses cell growth in human oral cancer cells.

BACKGROUND: Danshen is a common traditional Chinese medicine used to treat neoplastic and chronic inflammatory diseases in China. However, the effects of Danshen on human oral cancer cells remain relatively unknown. This study investigated the antiproliferative effects of a Danshen extract on human oral cancer SAS, SCC25, OEC-M1, and KB drug-resistant cell lines and elucidated the possible underlying mechanism. METHODS: We investigated the anticancer potential of the Danshen extract in human oral cancer cell lines and an in vivo oral cancer xenograft mouse model. The expression of apoptosis-related molecules was evaluated through Western blotting, and the concentration of in vivo apoptotic markers was measured using immunohistochemical staining. The antitumor effects of 5-fluorouracil and the Danshen extract were compared. RESULTS: Cell proliferation assays revealed that the Danshen extract strongly inhibited oral cancer cell proliferation. Cell morphology studies revealed that the Danshen extract inhibited the growth of SAS, SCC25, and OEC-M1 cells by inducing apoptosis. The Flow cytometric analysis indicated that the Danshen extract induced cell cycle G0/G1 arrest. Immunoblotting analysis for the expression of active caspase-3 and X-linked inhibitor of apoptosis protein indicated that Danshen extract-induced apoptosis in human oral cancer SAS cells was mediated through the caspase pathway. Moreover, the Danshen extract significantly inhibited growth in the SAS xenograft mouse model. Furthermore, the Danshen extract circumvented drug resistance in KB drug-resistant oral cancer cells. CONCLUSION: The study results suggest that the Danshen extract could be a potential anticancer agent in oral cancer treatment.

Comparative Proteomic Analysis of Rat Bronchoalveolar Lavage Fluid after Exposure to Zinc Oxide Nanoparticles.

Zinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanomaterials in consumer products and industrial applications. As a result of all these uses, this has raised concerns regarding their potential toxicity. We previously found that candidate markers of idiopathic pulmonary fibrosis and lung cancer were significantly up-regulated in rat bronchoalveolar lavage fluid (BALF) following exposure to ZnO NPs by using a liquid chromatography (LC)-based proteomic approach. To achieve comprehensive protein identification analysis, we conducted the two-dimensional gel electrophosis (2-DE)-based proteomic workflow to analyze the differences in BALF proteins from rats that had been exposed to a high dose of 35 nm ZnO NPs. A total of 31 differentially expressed protein spots were excised from the gels and analyzed by nanoLC-tandem mass spectrometry (MS/MS). Gene ontology (GO) annotation of these proteins showed that most of the differentially expressed proteins were involved in response to stimulus and inflammatory response processes. Moreover, pulmonary surfactant-associated protein D and gelsolin, biomarkers of idiopathic pulmonary fibrosis, were significantly up-regulated in rat BALF after ZnO NPs exposure (2.42- and 2.84-fold, respectively). The results obtained from this present study could provide a complementary consequence with our previous study and contribute to a better understanding of the molecular mechanisms involved in ZnO NP-induced lung disorders.

Melatonin exerts anti-oral cancer effect via suppressing LSD1 in patient-derived tumor xenograft models.

Aberrant activation of histone lysine-specific demethylase (LSD1) increases tumorigenicity; hence, LSD1 is considered a therapeutic target for various human cancers. Although melatonin, an endogenously produced molecule, may defend against various cancers, the precise mechanism involved in its anti-oral cancer effect remains unclear. Patient-derived tumor xenograft (PDTX) models are preclinical models that can more accurately reflect human tumor biology compared with cell line xenograft models. Here, we evaluated the anticancer activity of melatonin by using LSD1-overexpressing oral cancer PDTX models. By assessing oral squamous cell carcinoma (OSCC) tissue arrays through immunohistochemistry, we examined whether aberrant LSD1 overexpression in OSCC is associated with poor prognosis. We also evaluated the action mechanism of melatonin against OSCC with lymphatic metastases by using the PDTX models. Our results indicated that melatonin, at pharmacological concentrations, significantly suppresses cell proliferation in a dose- and time-dependent manner. The observed suppression of proliferation was accompanied by the melatonin-mediated inhibition of LSD1 in oral cancer PDTXs and oral cancer cell lines. In conclusion, we determined that the beneficial effects of melatonin in reducing oral cancer cell proliferation are associated with reduced LSD1 expression in vivo and in vitro.

Triptolide represses oral cancer cell proliferation, invasion, migration, and angiogenesis in co-inoculation with U937 cells.

OBJECTIVES: Advanced oral cancer is a major public health concern because of a lack of effective prevention and treatment. Triptolide (TPL), a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, has been demonstrated to possess strong anticancer properties. In this study, we investigated whether TPL exerts anticancer effects on the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Human macrophage-like U937 cells were co-inoculated with oral cancer SAS cells in a noncontact transwell coculture system. Cytokine expression was detected using ELISA, and cell proliferation was detected using methylene blue. RNA levels were detected using qPCR. Protein levels were detected using Western blot analysis. In vivo experiments involved using xenografted NOD/SCID mice. RESULTS: Our results demonstrated that TPL inhibited the growth of SAS cells co-inoculated with U937 cells in vitro and in vivo. TPL inhibited the invasion, migration ability, and angiogenesis of SAS cells co-inoculated with U937 cells. Expression of cytokines IL-6, IL-8, and TNF-α was induced by co-inoculation, but TPL repressed their expression. CONCLUSION: TPL suppressed the expression of cytokines IL-6, IL-8, and TNF-α, as well as tumor growth, invasion, migration, and angiogenesis in the co-inoculation of human tongue cancer cells with macrophage-like U937 cells. CLINICAL RELEVANCE: TPL is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating tumor-associated macrophages in a tumor microenvironment of HNSCC.

Anticancer efficacy of unique pyridine-based tetraindoles.

Results of previous studies demonstrated that the tetraindole, SK228, which has a high lipid but low water solubility, displayed moderate anticancer efficacy in a xenograft model of breast cancer. This finding led to the proposal that new, pyridine based tetraindole (PBT) analogs of SK228, containing tetraindole moieties distributed about central protonated pyridine cores, would have enhanced bioavailabilities and anticancer efficacies. Among the PBTs prepared and subjected to biological studies, 3f (FCW81) was observed to display the highest antiproliferative activity against the two triple negative breast cancer (TNBCs) cell lines, MDA-MB-231 and BT549. In addition, its mode of action was shown to involve G2/M arrest of the cell cycle along with the promotion of increased levels of cyclin B1 and p-chk2 and a decreased level of p-cdc2. DNA damage and induction of apoptosis caused by FCW81 was found to be associated with a decrease in DNA repair. Significantly, FCW81 displays therapeutic efficacy in a xenograft model of human breast cancer by not only serving to inhibit markedly the growth of cancer cells but also to block effectively cancer cell metastasis. Collectively, the results of these studies have led to the identification of novel pyridine-tetraindole based anticancer agents with potential use in TNBC therapy.

Association of reduced tumor necrosis factor alpha, gamma interferon, and interleukin-1beta (IL-1beta) but increased IL-10 expression with improved chest radiography in patients with pulmonary tuberculosis.

Mycobacterium tuberculosis infection is a major world health issue. The early identification of patients at risk for a poor response to anti-M. tuberculosis therapy would help elucidate the key players in the anti-M. tuberculosis response. The objective of the present study was to correlate the modulation of cytokine expression (interleukin-1 [IL-1], IL-6, IL-8, IL-10, IL-12, gamma interferon [IFN-gamma], interferon-inducible protein [IP-10], and monocyte chemotactic protein 1 [MCP-1]) with the clinical response to 2 months of intensive therapy. From January to December 2007, 40 M. tuberculosis-infected patients and 40 healthy patients were recruited. After exclusion for diabetes, 32 patients and 36 controls were analyzed. The clinical responses of the M. tuberculosis-infected patients on the basis of the findings of chest radiography were compared to their plasma cytokine levels measured before and after 2 months of intensive anti-M. tuberculosis therapy and 6 months of therapy with human cytokine antibody arrays. Chest radiographs of 20 of 32 M. tuberculosis-infected patients showed improvement after 2 months of intensive therapy (early responders), while the M. tuberculosis infections in 12 of 32 of the patients resolved after a further 4 months (late responders). The levels of expression of TNF-alpha, MCP-1, IFN-gamma, and IL-1beta were decreased; and the level of IL-10 increased in early responders. After adjustment for age, gender, and the result of sputum culture for M. tuberculosis, significant differences in the levels of MCP-1 and IP-10 expression were observed between the early and the late responders after 2 months of intensive anti-M. tuberculosis therapy. Due to the interpatient variability in IP-10 levels, intrapatient monitoring of IP-10 levels may provide more insight into the M. tuberculosis responder status than comparison between patients. Plasma MCP-1 levels were normalized in patients who had resolved their M. tuberculosis infections. Further studies to evaluate the association of the modulation in MCP-1 levels with early and late responses are warranted.