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PubMedDate not supplied

Human cancer detection and immunotherapy with conjugated and non-conjugated monoclonal antibodies.

Classical therapeutic modalities such as surgery, radiation and chemotherapy not only fail to cure the majority of neoplastic disease, but their employment also leads to severe and debilitating side effects. The severe cancer related morbidity is often associated with the use of radiation and chemotherapy, making them less than ideal forms of therapy. Entirely new approaches to cancer therapy that are tumor cell directed, and specifically lethal to malignant cells and less toxic to normal tissues are being observed and developed, adhering to the old prayer "Destroy the diseased tissues, preserve the normal." Following the initial advances of Ehrlich, immunotherapy as a fourth modality of cancer therapy has already been developed and proven to be quite effective. Unfortunately, the cancer cell population is not a static entity, but rather a continually changing one. Considerable variations have been determined between individual malignant cells. Our strong belief is that it is necessary for present-day clinical oncologists to become aware of the existence of immunotherapy and learn how to employ it in order to improve the efficacy and decrease the side effects of modern cancer therapy. The development of hybridoma technology and the advances in monoclonal antibody (MoAB) production have revitalized the concept concerning the existence of cancer cell-targeted, specific "magic bullets". In addition, a variety of different agents (e.g. toxins, radionuclides, chemotherapeutic drugs) have been conjugated to mouse and human MoABs for selective delivery to cancer cells. Preclinical observations in athymic, nude mice using xenografted human cancers and mouse, anti-human MoABs were more than impressive and have lead to several clinical trials. Strategies for the employment of MoABs for cancer immunotherapy include: a) Immune reaction directed destruction of cancer cells; b) Interference with the growth and differentiation of malignant cells; c) Antigen epitope directed transport of anti-cancer agents to malignant cells; d) Anti-idiotype vaccines. Phase I studies have established the safety of employing immunoconjugates in humans, but the therapeutic results were less impressive. The clinical use of mouse MoABs in humans is limited due to the development of an anti-globulin immune response to the non-human immunoglobulins by the human host. Genetically engineered chimeric human-mouse MoABs have been developed by replacing the mouse Fc region with the human constant region. Moreover, the framework regions of variable domains of rodent immunoglobulins were also experimentally replaced by their human equivalents. These antibodies can also be designed to have specificities and effector functions determined by researchers, which may not appear in nature. The astonishing immunophenotypic (IP) heterogeneity of cancer cells, the different cytotoxic activity associated with the moiety linked to given MoABs, and mostly the impressive genetic modulation capabilities of cancer cells still remain as yet unsolved difficulties in the present immunotherapy of human cancer. Antibodies with two binding ends (bispecific antibodies) provide a great improvement in targeting cancer cells. The existing inadequacies of MoABs in immunotherapy may also be improved by increasing their efficiency with chemical coupling to various agents such as bacterial or plant toxins, radionuclides or cytotoxic drugs. In writing this review article, one of our main goals is to encourage further clinical research with the use of genetically engineered rodent MoABs and various immunoconjugates in the treatment of human cancer, as well as the combination of such immunotherapy with the three conventional modalities of therapy. Finally, we propose that MoAB-based immuno-therapy be accepted as a conventional form of therapy and employed not only in terminal cancer patients, but also, for instance, during and following surgical resection.

Animals↗

PubMed2006

Efficacy and safety of linezolid in multidrug resistant tuberculosis (MDR-TB)--a report of ten cases.

OBJECTIVES: Multidrug resistant tuberculosis (MDR-TB) is an increasing problem in many parts of the world and in Norway the increase has been substantial since 1998. New therapies for MDR-TB have not been introduced since the fluoroquinolones in the 1970s. The cure rate of this disease has been reported to be lower than for non-drug resistant TB, and the use of new experimental drugs in combination therapy is warranted. METHODS: Ten consecutive patients with culture proven MDR-TB were treated with the novel antibiotic drug linezolid in combination regimens for 6-40 (median 17) weeks and followed up 11-50 (median 24) months after end of treatment. All strains were sensitive to linezolid with MIC<4 mg/l. Treatment was given as direct observed therapy (DOT) and sputum cultures, blood chemistry and neurologic examination were undertaken on a regular basis. RESULTS: Nine patients were cured, one patient with poor adherence to treatment and advanced AIDS died. Seven of 10 patients experienced serious adverse events, which led to withdrawal of linezolid in all seven. Six patients developed peripheral neuropathy and five patients bone marrow depression, blood transfusions were given to three patients and in all five patients bone marrow function normalized after cessation of linezolid. Peripheral neuropathy was not fully reversed in all patients. CONCLUSION: Linezolid seems highly active in combination treatment of MDR-TB. Cultures became negative 10-37 days after the introduction of the drug. However, peripheral neuropathy and bone marrow depression led to linezolid withdrawal in seven patients, and neuropathy may not be fully reversible in all patients.

Acetamides↗

PubMed1993

A sensory role for neuronal growth cone filopodia.

The dynamic nature of neuronal growth cone filopodia led to the suggestion that the primary function of filopodia is to sample their immediate environment, responding to and transducing environmental signals that affect growth cone behaviour and shape. Filopodia seem well suited to serve as antenna-like sensors, their broad span allows sampling of information over a greatly enhanced radius, and forward-projecting filopodia encounter potential cues in the molecular terrain long before the advancing growth cone itself. Filopodia in culture can serve structural roles, exert mechanical tension and selectively adhere to their surrounding. Whether or not filopodia have a general sensory role has not been tested directly, largely because of their small size, which limits an electrophysiological approach, and their integral relationship with the parent growth cone, which prevents resolution of their different functions. Here we use surgical procedures to isolate individual filopodia from their parent growth cone and, by monitoring their morphology and calcium second messenger systems, we show that neuronal growth cone filopodia contain signal transduction mechanisms that allow autonomous responses and the transmission of distant environmental information to their parent growth cone.

Acetylcholine↗

PubMed2004

The evolution to stool DNA testing for colorectal cancer.

Despite a variety of screening strategies and recent trends showing death rate stabilization, colorectal cancer still remains the second leading cause of overall cancer death. Current screening tools suffer from performance limitations, low patient acceptability, and marginal reliable access within the health care system. Noninvasive strategies present the lowest risk with the highest potential for patient satisfaction. However, serious implementation barriers exist requiring consistent programmatic screening, strict patient adherence, and poor sensitivity for adenomas. Colonoscopy remains an invasive screening test with the best sensitivity and specificity, but faces large financial costs, manpower requirements, patient access and adherence. Development of advanced molecular techniques identifying altered DNA markers in exfoliated colonocytes signify early or precancerous growth. Stool-based DNA testing provides an entirely noninvasive population-based screening strategy which patients can perform easier than faecal occult blood testing (FOBT). Large-scale prospective randomized control trials currently pending should help characterize accurate test performance, screening intervals, cost-effectiveness, direct comparison to FOBT and analysis of patient adherence. As tumour development pathways and potential target genes are further elucidated, refinements in multi-assay stool-based DNA testing portend enhanced test characteristics to detect and treat this genetically heterogeneous disease.

Biomarkers, Tumor↗

PubMed2004

Effectiveness and tolerability of a once-daily amprenavir/ritonavir-containing highly active antiretroviral therapy regimen in antiretroviral-naïve patients at risk for nonadherence: 48-week results after 24 weeks of directly observed therapy.

OBJECTIVES: To determine the safety and effectiveness of a once-daily highly active antiretroviral therapy (HAART) regimen in patients at risk for poor adherence using directly observed therapy (DOT) for 24 weeks followed by weekly phone contact for another 24 weeks. METHODS: A prospective, open-label pilot study was carried out. Antiretroviral-naïve patients with advanced HIV disease were treated with once-daily amprenavir 1200 mg, ritonavir 200 mg, didanosine 400 mg and lamivudine 300 mg. After 24 weeks, DOT was substituted by weekly phone contact. Measurements of viral load and CD4 cell count, and safety laboratory measurements, were taken regularly for 48 weeks. RESULTS: Twenty-two patients were enrolled in the study, of whom 19 completed at least 4 weeks of treatment. Seventeen patients completed 24 weeks and 13 completed 48 weeks. None discontinued treatment as a result of adverse events. The median baseline HIV viral load was 5.29 log(10) HIV-1 RNA copies/mL and the median CD4 cell count was 20 cells/microL. At weeks 24 and 48, 74% of the patients had viral loads <400 copies/mL. At 48 weeks, the median decrease in viral load from baseline was 3.06 log(10) copies/mL, and the median increase in CD4 cell count was 118 cells/microL. The median trough plasma amprenavir concentrations at weeks 1 and 24 were 1.87 and 1.42 microg/mL, respectively. CONCLUSIONS: This study suggests that DOT followed by weekly patient contact results in good treatment outcome in this challenging population. The median trough plasma amprenavir concentrations were above the effective concentration of drug that resulted in 90% inhibition of viral load in vivo (EC(90)) for wild-type HIV.

Adult↗

PubMed1997

Enhancing adherence following abnormal Pap smears among low-income minority women: a preventive telephone counseling strategy.

BACKGROUND: Although the incidence of precancerous conditions of the cervix has recently been increasing, prompt initial and long-term follow-up care can effectively reduce unnecessary morbidity and mortality. For example, the 4-year survival rates among those individuals at greatest risk for cervical cancer (i.e., minority women of low socioeconomic status) approach 95% with early detection. Women who present with advanced disease have a much poorer outlook (0%-39% survival). Yet, high-risk individuals are least likely to adhere to recommended diagnostic regimens. PURPOSE: We tested the effectiveness of a brief telephone counseling intervention directed to low-income, inner-city women after they had received an abnormal Pap smear result. The women were counseled on the importance of having an initial and 6-month repeat follow-up diagnostic procedure (i.e., colposcopic examination of the cervix). METHODS: A randomized trial design was used to compare the effects on these women of telephone counseling with (n = 192) or without (n = 203) a booster counseling telephone call prior to the appointment for a repeat colposcopy 6 months later, with a telephone appointment confirmation/reminder call (n = 216) and with standard care (i.e., no telephone contact) (n = 217). The telephone counseling protocol probed for and addressed three psychologic barriers to adherence (i.e., attendance at appointment for colposcopy examination): 1) encoding/expectancy (e.g., did the patient understand her risk of developing cervical cancer?); 2) affective/emotional (e.g., was the woman worried about the condition and its consequences?); and 3) self-regulatory/practical (e.g., was the woman likely to forget medical appointments?). Logistic regression was used to analyze the effects of the intervention group and the type of psychologic barriers elicited on colposcopy adherence. RESULTS: The results of logistic regression analysis (using those who received an appointment confirmation/reminder telephone call as the comparison group) revealed that telephone counseling produced significantly higher adherence rates to the initial colposcopy visit compared with telephone confirmation (300 [76%] of 395 women versus 147 [68%] of 216; odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.04-2.17). Additionally, standard care resulted in significantly lower adherence rates than did telephone confirmation (109 [50%] of 217 women versus 147 [68%] of 216; OR = 0.47; 95% CI = 0.32-0.73). Regarding attendance at the 6-month repeat colposcopy appointments, the 80 patients who had received telephone counseling prior to the initial visit (and were recommended for follow-up colposcopy) were significantly more likely to adhere than were the 47 patients who had received telephone confirmation (49 [61%] of 80 women versus 17 [36.2%] of 47; OR = 2.70; 95% CI = 1.15-6.51). The 6-month adherence rates for patients in the telephone confirmation group and the standard care group (n = 30) were low and did not differ significantly (17 [36.2%] of 47 women versus nine [30.0%] of 30; OR = 1.08; 95% CI = 0.40-2.89). Forgetting medical appointments (OR = 0.31; 95% CI = 0.19-0.51) and having scheduling conflicts (OR = 0.45; 95% CI = 0.28-0.72) were also associated with lower rates of adherence. CONCLUSION: The use of telephone counseling appears to be an effective strategy for enhancing initial and long-term adherence to a follow-up cervical diagnostic procedure in a traditionally underserved population. Patients who respond to a positive Pap test result with a particular profile of psychologic barriers may require more intensive and targeted counseling interventions.

Colposcopy↗

PubMed1988

Estramustine inhibits monocyte phagocytosis.

Estramustine phosphate (EMP) influence on human monocyte phagocytosis of fluorescein isothiocyanate (FITC)-labeled yeast cells was measured in vitro. The method used, a modification of Hed's technique (FEMS Microbiol Lett 1:357, 1977), can differentiate between yeast cell engulfment and adherence to the phagocytotic cell surface. EMP is now accepted in the treatment of advanced prostatic carcinoma. In concentrations corresponding to the clinical situation (20-40 micrograms/ml), it dramatically inhibited the process of phagocytosis. The engulfment phase was inhibited, whereas cell adherence was less affected. This might be due to direct interaction with the microtubule system. The effects were totally reversible. In contrast, the metabolites estradiol and normustine did not affect engulfment of yeast cells, either as single agents or combined. The results demonstrate that the EMP complex caused an impaired phagocytosis, which could be of pathophysiological significance in the compromised cancer patients.

Cell Adhesion↗

PubMed1994

Resection for cure of carcinoma of the colon directly invading the duodenum or pancreatic head.

BACKGROUND: Approximately 10 percent of carcinomas of the colon and rectum adhere to adjacent organs or structures, which rarely include the duodenum or pancreas. STUDY DESIGN: To confirm the importance of aggressive operative management in patients with locally advanced carcinoma of the colon invading the duodenum or pancreatic head, we reviewed the medical records of 12 patients who underwent an extended resection for a right-sided carcinoma of the colon involving the duodenum or the pancreatic head, or both. RESULTS: All patients underwent an extended right hemicolectomy, including en bloc pancreaticoduodenectomy (seven patients) or lateral duodenectomy (five patients). The mean operative blood loss was 627 mL, and there were no postoperative deaths. Malignant invasion of the duodenum or pancreas was confirmed in all 12 patients, but only three (25 percent) had lymph node metastases. The median survival period for all 12 patients was 32 months. However, the median survival period for the eight patients still alive without recurrent or metastatic disease was 42 months. CONCLUSIONS: In patients with locally advanced carcinoma of the colon involving the duodenum or pancreatic head long-term survival can be achieved by en bloc resection.

Adenocarcinoma↗

PubMed1987

Constitutional background to the Social Security Act of 1935.

In June 1937, the Senate Judiciary Committee reported unfavorably on Roosevelt's Court-packing plan and the bill was effectively killed. In the same month, Justice Van Devanter retired and gave Roosevelt his first opportunity to make an appointment to the Supreme Court. Over the following 6 years, Roosevelt made seven more appointments to the Court, and in the years that followed the Court continued in the direction boldly advanced in the spring of 1937. A residual effect of the taxing-spending construction of the old-age insurance provisions of the Social Security Act of 1935 has been the Court's continued adherence to the view that social security programs consist of separate taxing and spending provisions and are not, constitutionally speaking, social insurance programs. The issue has arisen in both a due process context and an equal protection context. But it is unlikely that the decisions reached in these contexts would have been different had the old-age insurance program been drafted as an earned-benefits program pursuant to the commerce power. Of course, the Court's decisions in the social security cases represented a significant constitutional development in establishing the breadth of Congress' powers to tax and spend for the general welfare. The decisions not only cleared the way for other general welfare programs, but more fundamentally provided the Federal Government with the substantive power and institutional flexibility to respond to the changing needs of the Nation.

History, 20th Century↗

PubMed2006

Rigor mortis and the epileptology of Charles Bland Radcliffe (1822-1889).

Charles Bland Radcliffe (1822-1889) was one of the physicians who made major contributions to the literature on epilepsy in the mid-19th century, when the modern understanding of the disorder was beginning to emerge, particularly in England. His experimental work was concerned with the electrical properties of frog muscle and nerve. Early in his career he related his experimental findings to the phenomenon of rigor mortis and concluded that, contrary to the general belief of the time, muscle contraction depended on the cessation of nerve input, and muscle relaxation on its presence. He adhered to this counter-intuitive interpretation throughout his life and, based on it, produced an epileptology that was very different from those of his contemporaries and successors. His interpretations were ultimately without any direct influence on the advance of knowledge. However, his idea that withdrawal of an inhibitory process released previously suppressed muscular contractile powers, when applied to the brain rather than the periphery of the nervous system, permitted Hughlings Jackson to explain certain psychological phenomena that accompany or follow some epileptic events. As well, Radcliffe was one of the chief early advocates for potassium bromide, the first effective anticonvulsant.

England↗

PubMed1994

Phenotypic analysis of nylon-wool-adherent suppressor cells that inhibit the effector process of tumour cell lysis by lymphokine-activated killer cells in patients with advanced gastric carcinoma.

The causes of down-regulation of cytotoxic immune responses in cancer patients have not been fully evaluated. We previously demonstrated that T-cell-growth-factor-activated peripheral blood lymphocytes (PBL) with the surface phenotype CD8+ CD11b-, from patients with widespread metastasis of gastric carcinoma, inhibited the effector process of lymphokine-activated-killer(LAK)-cell-mediated cytolysis. In this study, we examined suppressor cell activity in freshly prepared PBL from 18 patients with advanced gastric carcinoma, and 10 normal healthy individuals. The suppressor cell activity was assayed by recording whether or not PBL inhibited directly the effector process of LAK cell cytotoxicity. Most of the PBL suspensions from cancer patients showed that they contained a population of cells that can directly inhibit the effector phase of tumor cell lysis of the cytotoxic cells. To analyze further the PBL responsible for the suppression, the cells were passed over a nylon-wool column. Nylon-wool-adherent cells significantly augmented the suppression, while the cells passing through abrogated the suppressive effect. Most nylon-wool-adherent cells from 10 normal healthy controls did not inhibit the cytotoxic reaction. To determine further the suppressor-effector population in nylon-wool-adherent cells, negative-selection studies using CD8-, CD4- or CD11b-coated magnetic beads, and positive-selection studies using CD8- or CD4-coated magnetic beads were performed. Finally the results suggest that the suppressor-effector cells comprise at least two different surface phenotypes: CD8+ T and CD8-CD11b+ cells. The possible role of CD4+ T cells and HLA-DR+ LeuM3+ macrophages as suppressor cells was ruled out in nylon-wool-adherent cells. CD8+ T and possibly CD8-CD11b+ cells apparently suppressed the efferent limb of the antitumor immunity. The selective immune suppression mediated by these cells may partly be concerned with escape mechanisms of gastric carcinoma from the host immune surveillance system.

Adult↗

PubMed1999

Adhesion-dependent multicellular drug resistance.

Herein we review studies demonstrating resistance manifested at the multicellular level, a phenomenon referred to as intrinsic or acquired multicellular resistance (MR). In addition, due to the fact that such resistance can be recapitulated in vitro only when cells are adhered to one another in a three-dimensional culture context, we examine the roles of cell adhesion molecules and how they may contribute directly or indirectly to MR. Finally, we suggest an experimental approach to circumvent MR in the treatment of advanced, aggressive ascites tumors.

Animals↗

PubMed1978

Neural factors in experimental degenerative arteriopathy.

Intermittent electrical stimulation of the lateral hypothalamus of rats performed for 30 min to 6 hr, results in hyperlipidemia and endothelial cell damage of the aorta and coronary arteries. Hyperlipidemia is related to transient biliary obstruction elicited by hypothalamic stimulation and is characterized by elevation of the cholesterol, phospholipid, and triglyceride fractions. Endothelial cell damage is observed ultrastructurally as plasma membrane degeneration with detachment and the formation of large spaces ("vacuoles"). Thus, neural factors may be implicated in inducing conditions associated with early atherogenesis. Stimulation carried out for longer time intervals would be expected to produce more advanced lesions. However, the role of neural transmission per se (i.e., without hyperlipidemia) in producing arteriopathy is not clearly defined from these experiments. In rats, the lesser splanchnic nerve forms the major innervation of the abdominal aorta. In animals fed normal diets, chronic intermittent stimulation of this nerve (up to 3 weeks) resulted in advanced arteriosclerotic changes with intimal fibrosis and calcification. On histologic examination, lipid deposits appeared to be absent from these lesions. Animals stimulated for shorter periods of time exhibited earlier changes associated with atherogenesis, such as endothelial damage, elastic reduplication, and adherent microthrombi. Thus, direct neural transmission, especially if excessive, plays a role in producing arteriopathy. Hyperlipidemia, if persistent, could modify these lesions so that they would accumulate plasma lipids. Experiments to test this hypothesis are currently in progress.

Animals↗

PubMed1993

Role of interleukin-1 inhibitory molecules in therapy of acute and chronic myelogenous leukemia.

The poor outcome of conventional therapy of acute and chronic myelogenous leukemias (AML and CML) has prompted several groups to investigate new therapeutic directions. Data from various laboratories, including our own, indicate that both normal and leukemia precursors proliferate in response to growth factors. Furthermore, it has been shown that AML blasts, low-density cells from CML patients with advanced disease, and cultured bone marrow-adherent layers from CML blast crisis patients produce interleukin 1 (IL-1); this molecule may play a pivotal role in driving leukemia cell proliferation through autocrine or paracrine pathways. We have therefore hypothesized that interruption of the IL-1-mediated growth-stimulatory mechanism may suppress leukemia precursor multiplication. In searching for IL-1-inhibitory molecules that may be used clinically, we have investigated the in vitro effects of various IL-1 inhibitors including IL-1 receptor antagonist, soluble IL-1 receptors, and interleukin 4. Our studies suggest that IL-1 inhibitors can suppress clonogenic growth of cultured AML and CML progenitors and may hence be exploitable in clinical trials.

Animals↗

PubMed2005

PIK3CA mutations in advanced ovarian carcinomas.

PIK3CA belongs to the phosphatidylinositol 3-kinases (PI3Ks) family, which play an important role in proliferation, adherence, transformation and cell survival through the PI3K/AKT signaling pathway. Somatic activating mutations of this gene have recently been detected in several types of cancers. In the present study, 109 advanced ovarian carcinomas were analyzed for PIK3CA mutations in exon 9 and exon 20 by direct sequencing. Activating missense mutations were observed in 4 of the 109 tumors in addition to one variant leading no change of the PIK3CA protein. Two of the cases with mutations were mucinous and clear cell tumors, suggesting that PIK3CA mutations are more common in these rare histological types.

Adenocarcinoma, Clear Cell↗

PubMed2002

En bloc pancreaticoduodenectomy for right colon cancer invading adjacent organs.

BACKGROUND AND OBJECTIVE: Surgical treatment of colorectal cancer needs an extended resection of the tumor en block with invaded organs. There is little information about the surgical treatment of right-sided colon carcinoma directly involving duodenum and pancreas. Our objective is to report our experience with three patients who underwent en bloc pancreaticoduodenectomy and hemicolectomy for locally advanced right colon cancer. METHODS: Retrospective review of clinical records of patients with colon cancer. RESULTS: Three patients with right colon cancer adherent to adjacent organs underwent en block surgery. No operative deaths occurred. All patients are alive without evidence of disease at 10, 30, 113 months of follow-up, respectively. CONCLUSION: Locally advanced right-sided colon cancer can be safely treated with en bloc pancreaticoduodenectomy and colectomy with excellent long-term results.

Adult↗

PubMed2002

Initial management of temporomandibular disorders.

The existing dental literature does not support the superiority of any one type of treatment to manage TMD. Few studies meet rigorous scientific standards of the randomized clinical trial. This has led to enormous controversy. The initial management of TMD does not have to be controversial. Noninvasive, reversible modalities can be employed that carry very little risk and a high degree of success (Table 4). The success rate of this approach has been studied and determined to be 75% to 90%. Of course, not every patient will get better with this approach. For those who do not improve more advanced techniques must be used, and referral to specialists in TMD, neurology, and rehabilitation medicine may be required. A few patients will need surgery. Initial treatment of TMD requires relatively simple modalities, such as patient education, adherence to a soft diet, reducing oral habits, self-directed home physical therapy, muscle relaxation, the use of medication, and the proper use of bite plates. The majority of TMD patients will respond successfully to these basic treatments.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2025

Advancing the fight against tuberculosis: integrating innovation and public health in diagnosis, treatment, vaccine development, and implementation science.

Tuberculosis (TB) remains one of the leading causes of infectious disease mortality worldwide, increasingly complicated by the emergence of drug-resistant strains and limitations in existing diagnostic and therapeutic strategies. Despite decades of global efforts, the disease continues to impose a significant burden, particularly in low- and middle-income countries (LMICs) where health system weaknesses hinder progress. This comprehensive review explores recent advancements in TB diagnostics, antimicrobial resistance (AMR surveillance), treatment strategies, and vaccine development. It critically evaluates cutting-edge technologies including CRISPR-based diagnostics, whole-genome sequencing, and digital adherence tools, alongside therapeutic innovations such as shorter multidrug-resistant TB regimens and host-directed therapies. Special emphasis is placed on the translational gap-highlighting barriers to real-world implementation such as cost, infrastructure, and policy fragmentation. While innovations like the Xpert MTB/RIF Ultra, BPaLM regimen, and next-generation vaccines such as M72/AS01E represent pivotal progress, their deployment remains uneven. Implementation science, cost-effectiveness analyses, and health equity considerations are vital to scaling up these tools. Moreover, the expansion of the TB vaccine pipeline and integration of AI in diagnostics signal a transformative period in TB control. Eliminating TB demands more than biomedical breakthroughs-it requires a unified strategy that aligns innovation with access, equity, and sustainability. By bridging science with implementation, and integrating diagnostics, treatment, and prevention within robust health systems, the global community can accelerate the path toward ending TB.

diagnostic innovation↗